QN - USP - Rev 06

QUINAPRIL HYDROCHLORIDE USP
OPEN PART

OPEN PART FOR

CUSTOMER
(In CTD format)
QUINAPRIL
HYDROCHOLRIDE USP
Référence No : AIL/QN/USP/AP/06/2020-01-08
AARTI INDUSTRIES LIMITED

71, Udyog Kshetra, Mulund Goregaon Link Road,
Mulund (W), Mumbai – 400 080, INDIA
Tel: 91-22-67976666, 25918195
Fax: 91-22-67976660
Web site: www.aarti-industries.com
January, 2020
OPEN PART

MODULE 3
January, 2020
OPEN PART

3.1 TABLE OF CONTENTS
Section Details Pages

3.1 Table of contents 1
3.2.S.1 General information 1
3.2.S.1.1 Nomenclature 1
3.2.S.1.2 Structure 1
3.2.S.1.3 General properties 1
3.2.S.2 Manufacture 1
3.2.S.2.1 Manufacturer 1
3.2.S.2.2 Description of manufacturing process & process controls 1-10
3.2.S.2.3 Control of materials 1-17
3.2.S.2.4 Control of critical steps and intermediates 1
3.2.S.2.5 Process validation and/or evaluation 1
3.2.S.2.6 Manufacturing process development 1
3.2.S.3 Characterization 1
3.2.S.3.1 Elucidation of structure and other characteristics 1-20
3.2.S.3.2 Impurities 1-18
3.2.S.4 Control of drug substance 1
3.2.S.4.1 Specification 1-4
3.2.S.4.2 Analytical procedure 1-17
3.2.S.4.3 Validation of analytical procedures 1-617
3.2.S.4.4 Batch analysis 1-4
3.2.S.4.5 Justification of specification 1
3.2.S.5 Reference standards or materials 1-7
3.2.S.6 Container closure system 1
3.2.S.6.1 Packing material specifications & test procedures 1-15
3.2.S.7 Stability 1
3.2.S.7.1 Stability summary and conclusion 1-188
3.2.S.7.2 Post approval stability study protocol and commitment 1-7
3.2.S.7.3 Stability data 1-28
January, 2020 3.1 TABLE OF CONTENTS Page 1

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3.2.S.1 GENERAL INFORMATION
Quinapril Hydrochloride belongs in a class of drugs called angiotensin converting

enzyme (ACE) inhibitors, which are used for treating high blood pressure and
heart failure and for preventing kidney failure due to high blood pressure and
diabetes.
Mechanism of Action:
Quinapril is de-esterified to the principal metabolite, quinaprilat, which is an
inhibitor of ACE activity in human subjects and animals. ACE is a peptidyl
dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor,
angiotensin II. Angiotensin II contracts the muscles of most arteries in the body,
including the heart, thereby narrowing the arteries and elevating the blood
pressure. In the kidney, the narrowing caused by angiotensin II also increases
blood pressure and decreases the flow of blood.
The effect of quinapril in hypertension and in congestive heart failure (CHF)

appears to result primarily from the inhibition of circulating and tissue ACE
activity, thereby reducing angiotensin II formation. Quinapril inhibits the
elevation in blood pressure caused by intravenously administered angiotensin I,
but has no effect on the pressure response to angiotensin II, norepinephrine or
epinephrine. Angiotensin II also stimulates the secretion of aldosterone from the
adrenal cortex, thereby facilitating renal sodium and fluid reabsorption. Reduced
aldosterone secretion by quinapril may result in a small increase in serum
potassium. In controlled hypertension trials, treatment with quinapril alone
resulted in mean increases in potassium of 0.07 mmol/L Removal of angiotensin
II negative feedback on renin secretion leads to increased plasma renin activity
(PRA).
The FDA approved Quinapril Hydrochloride in 1991.

The usual dose of Quinapril Hydrochloride is 5 - 40mg a day as a single dose or
two divided doses.
January, 2020 3.2.S.1 GENERAL INFORMATION Page 1

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3.2.S.1.1 NOMENCLATURE
International Quinapril Hydrochloride

nonproprietary name
Compendial name Quinapril Hydrochloride
Chemical names 3-Isoquinolinecarboxylic acid, 2-[2-[[1-
(ethoxycarbonyl)3-phenylpropyl] amino]-1-
oxopropyl]-1,2,3,4-tetrahydro-,
monohydrochloride, [3S-[2[R*(R*)],3R*]]
(S)-2-[(S)-N-[(S)-1-Carboxy-3-phenylpropyl]
alanyl]-1,2,3,4-tetrahydro-3-
isoquinolinecarboxylic acid, 1-ethyl ester,
monohydrochloride
Company code QN
Other non proprietary --
names
Us approved name Quinapril Hydrochloride
British approved name Quinapril Hydrochloride
CAS no. [82586 - 55 - 8]
January, 2020 3.2.S.1.1 NOMENCLATURE Page 1

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3.2.S.1.2 STRUCTURE
H3C O O
CH3
N .HCl
N
H
O
O OH
MOLECULAR FORMULA : C25H30N2O5.HCl
MOLECULAR MASS : 474.98
January, 2020 3.2.S.1.2 STRUCTURE Page 1

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3.2.S.1.3 GENERAL PROPERTIES
Description White to off white powder, with pink cast at

times.
Solubility Freely soluble in water
Melting point* Crystals from ethyl acetate-toluene 120-130°C,
Also white crystalline solid from acetonitrile
119-121.5C
UV-Maxima 205 nm in water.
Elemental Composition
C 63.32 %
H 6.81 %
N 5.72%
O 16.73 %
Isomerism S isomer
* Reference: Merck Index, 13th edition, 8139, page 1441.
January, 2020 3.2.S.1.3 GENERAL PROPERTIES Page 1

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3.2.S.2
MANUFACTURE
January, 2020 3.2.S.2 MANUFACTURE Page 1

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3.2.S.2.1 MANUFACTURER
Name and address of the manufacturing and testing site:
Aarti Industries Limited

Unit-IV, Plot No. E-50,
MIDC, Tarapur,
Taluka & District - Palghar
Pin-401 506
Maharashtra, INDIA
FEI Number: 3005256484

DUNS Number: 650459006
Contact persons:
Mr. Sanjay Gokhale (General Manager)
Tel. No.: +91-8983065452/ 8983035452
Email ID:sanjay.gokhale@aarti-industries.com
Mr. Shyamsundar Desai (DGM QA&QC)

Tel. No: +91-8983065452/ 8983035452
Email ID: shyamsundar.desai@aarti-industries.com
January, 2020 3.2.S.2.1 MANUFACTURER Page 1

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3.2.S.2.2 DESCRIPTION OF MANUFACTURING PROCESS & PROCESS
CONTROLS
3.2.S.2.2.1 BRIEF DESCRIPTION OF THE MANUFACTURING PROCESS
Manufacturing of Quinapril hydrochloride involves two steps.
Step I: Benzyl Quinapril Maleate:

In a reactor QN-II is charge with potable water and toluene. The pH of the
reaction mass is adjusted to 8.0 - 8.5 by sodium bicarbonate solution. The reaction
mass is settled and layer separation is done. The aqueous layer is extracted in
toluene, settled and layer separation is done followed by aqueous layer send to
ETP. Potable water is changed in the combined organic layer, settled and
separated the organic layer. S-1 compound and NBS is charge in the organic layer
at 21 ± 1°C along with AC compound in toluene and maintained for one hour.
The completion of reaction mass is checked by TLC (QN-II-NMT 1.0%). The
reaction mass is chilled to 0-5°C, after completion and maintained under stirring
for 1 hr. at 0-5°C. The solution is filtered using Agitated Nutsche filter.
The organic layer is washed twice with sodium bicarbonate solution followed by
potable water till pH of the aqueous layer is within 7.2 to 7.6. The organic layer is
cooled and treated with a solution of maleic acid in ethyl acetate at 40o-45oC and
maintained at the same temperature for two hours. Then the mass is cooled to 30o-
35oC, stirred for1 hour and the product is centrifuged the wet cake washing is
done using ethyl acetate and acetone. The reaction mass is filtered and dried using
Agitated Nutsche Filter and Dryer (AGNFD), water content should be less than
1.0% to give Benzyl quinapril maleate (QN III).
January, 2020 3.2.S.2.2 DESCRIPTION OF MANUFACTURING Page 1

PROCESS & PROCESS CONTROLS
OPEN PART

Step II: Quinapril Hydrochloride

Benzyl quinapril maleate (QN III) is reacted with sodium carbonate in water at
35o-40oC for 1 hour in presence of ethyl acetate till dissolution is complete, at a
pH of 9-10. If the pH is not within the range it is readjusted. After settling the two
layers for 45 minutes the organic layer is separated from the aqueous layer. The
organic layer is kept aside. The aqueous layer is extracted with ethyl acetate at 35-
40oC. The aqueous layer is then separated and discarded. The ethyl acetate
extract is mixed with the organic layer and then washed with water till the pH of
washing is between 7.3-7.7. The organic layer is then dried with anhydrous
sodium sulfate and the ethyl acetate is distilled under vacuum below 40oC till a
thick residual oil remains.
The thick oil is then dissolved in acetonitrile (i.e. DF) and the pH of the solution
is adjusted to 0.5-0.7 with DIPE-HCl at 0-5oC and stirred at the same temperature.
The temperature is the raised to 25-30oC. The solution is then hydrogenated in
presence of Palladium on carbon (wet) catalyst at 40-60 psi pressure of hydrogen
gas till HPLC analysis of a sample of the reaction mass withdrawn after 6 hours
shows the content of benzyl quinapril below 0.5%. After the reaction is complete
the reaction mass is filtered to remove the catalyst, the solvent is distilled out
under vacuum below 35C till a thick mass is obtained. The mass is dissolved in
DF at 50-55C clarified and cooled to 30-35C, The reaction mass is filtered and
dried using Agitated Nutsche Filter and Dryer (AGNFD) to give semi-dried
material. This semidried material is jet-milled and dried again in Vacuum Tray
Dryer (VTD) in two lots. The dried lots are mixed/blended and again dried till the
limit for water content and residual solvents is achieved. The completely dried
material is multi-milled to give Quinapril Hydrochloride.

OPEN PART

3.2.S.2.2.2 REACTION SCHEME
Step I: Benzyl Quinapril Maleate

COOCH 2C 6H 5
H 5C 2O O
HN .PTSA CH3 H 5C 2O O
Toluene CH3
NH COOH NBS
+ NH
N
AC Compound
O
Potable Water O OCH 2C 6 H 5
QN II S1 Compound NaHCO3 QN-II Base
Mol Wt. = 439 Mol wt. = 279 Maleic acid
Ethyl Acetate HC COOH Maleic
Acetone acid
HC COOH
H 5C 2O O
CH3 HC COOH
N
NH HC COOH
O
O OCH 2C 6H 5
Benzyl Quinapril Maleate (QN-III)

Mol wt. = 644
H 5C 2O O
CH3 H 5C 2O O
HC COOH
N Potable Water CH3
NH
HC COOH Na2CO3 N
O NH
Ethyl Acetate
O OCH 2 C 6 H 5 Acetonitrile O
Sodium sulphate O OCH 2 C 6 H 5
DIPE + HCl
Benzyl Quinapril Maleate QN IV
Mol wt. = 644 Mol Wt. = 528
DIPE+HCl 5% Pd/C/ Hydrogen
Acetonitrile Ethyl Acetate
H 5C 2O O
CH3
N
NH .HCl
O
O OH
Quinapril Hydrochloride
Mol wt. = 474.98

OPEN PART

3.2.S.2.2.3 FLOW CHART
Potable water
QN-II
Toluene Reactor
Saturated sodium bicarbonate solution Reaction M ass Sample for pH

Limit between
8.0-8.5
Organ ic Layer
Aqueous Layer
Toluene
Aqueous Layer
Organic Layer
Aqueous Layer
ETP
Potable water Organic Layer
Organ ic Layer
ETP
Aqueous Layer Twice
S-1 Compound
Organic Layer
NBS
AC compound Reaction M ass
M aintaining
Continued….

OPEN PART

Maintaining
Sample for TLC

Reaction Mass
Limit QN-II NMT 1.0%
Filtration
Filtrate
Saturated sodium Organic Layer

bicarbonate solution
Repeat twice
Organic Layer
ETP
Aqueous Layer
Potable Water Organic Layer
Sample for pH
Organic Layer
Limit between
7.2-7.6
Aqueous Layer
ETP
Continued….

OPEN PART

Maleic acid solution Organic Layer

in ethyl acetate
Maintaining
Reaction mass
Filtration
Ethyl acetate and acetone washing Wet cake
Ethyl acetate and acetone
Ethyl acetate Wet cake
Filtration
Ethyl acetate Wet cake

washing
Drying
Benzyl Quinapril
Sample for water content
Maleate
Limit NMT 1.0 %

OPEN PART

Potable water
Sodium carbonate Reactor
Benzyl Quinapril Maleate

Reaction Mass
Ethyl acetate
Stirring
Organic Layer
Sample for pH
Aqueous Layer
Limit between
9.0-10.0
Aqueous Layer
Ethyl acetate
Organic Layer
Aqueous Layer ETP
Potable water Organic Layer
Sample for pH
Organic Layer Limit between
7.3-7.7
Aqueous Layer
ETP
Sodium sulphate Organic Layer
Filtration (SF)
Continued…..

OPEN PART

Filtration
Ethyl acetate
Filtrate Check clarity
DF Thick oil
Reaction mass Check clarity
Cooling
Sample for pH
DIPE + HCl Reaction mass Limit between
0.5-0.7
Maintaining
Reaction mass
Hydrogenation
DF Flushing Sample for HPLC

Reaction mass Benzyl quinapril
Cat-B (wet) NMT 0.5 %
Catalyst filtration
DF distillation
Filtrate
Continued….

OPEN PART

DF Thick Mass Check clarity
Maintaining
DF Reaction mass
Filtration (AGNFD)
Repeat
Ethyl acetate wash Wet cake
Twice
Drying (AGNFD)
Semidried Material
Jet milling
Jet milled Material
Drying (VTD) in 2 lots
Blending of semidried
jet milled material
Blending of Dried
Sample for residual solvents
Material
& water content test
Mixing of Blended Sample for residual solvents

material
Sifting/Multi-mill
Quinapril HCl

OPEN PART

3.2.S.2.2.4 DETAILED DESCRIPTION OF THE PROCESS
Detailed description of the process is provided in section 3.2.S.2.2 of Restricted

Part.
BATCH NUMBERING SYSTEM:
QN-I/YYXXX
WHEREIN:
QN-I– Abbreviation for Benzyl Quinapril Maleate
YY – Year of Manufacture
XXX – Serial number of the batch.
Batch size: 120 kg input of QN-II
QN-YYXXX
WHEREIN:
QN – Abbreviation for Quinapril HCL
YY – Year of Manufacture
XXX – Serial number of the batch.
Batch size: 150 kg input of Benzyl Quinapril Maleate
3.2.S.2.2.5 REPROCESSING STATEMENT
If any batch fails to comply with the specifications it will be reprocessed by

repeating the purification process.
3.2.S.2.2.6 REWORK STATEMENT

Aarti has committed not to carryout reworking of Quinapril HCL.
Abbreviations: Used in Manufacturing Section.

(3S)-benzyl 1, 2, 3, 4-tetrahydroisoquinoline-3-
QN-II
carboxylate p-toluene sulphonate salt
N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-
S-1 Compound
alanine (ECPPA, hydride substance)
NBS 1-Hydroxybenzotriazole
AC Compound N, N Di-cyclohexyl carbodiimide

OPEN PART

3.2.S.2.3 CONTROL OF MATERIALS
3.2.S.2.3.1 RAW MATERIALS
The raw materials used in the manufacturing process of Quinapril HCl are:
Sr.
Raw Materials Code Remark
No
(3S)-Benzyl 1,2,3,4-
1 tetrahydroisoquinoline-3-car boxylate QN-II Starting Material
p-toluene sulfonate
2 Ethoxy carbonyl phenyl propyl alanine S1 Compound Starting Material
3 Sodium bicarbonate - Neutralizer
4 1-Hydroxybenzotriazole NBS Reagent
5 N, N Di-cyclohexyl carbodiimide AC Compound Reagent
6 Maleic acid - Reagent
7 Toluene - Solvent
8 Ethyl Acetate - Solvent
9 Acetone - Solvent
10 Sodium carbonate - Neutralizer
11 Benzyl Quinapril Maleate - Intermediate
12 Sodium sulphate - Reagent
13 5 % Palladium on carbon (wet) Cat-B (wet) Catalyst
14 Hydrogen Gas - Reagent
15 Nitrogen Gas - Inertizer
16 Acetonitrile DF Solvent
17 Di-isopropyl ether + HCL DIPE+HCL Reagent
18 Potable Water - Solvent
The detailed specification, test procedure and certificate of analysis for all
materials are given on Restricted Part.
January, 2020 3.2.S.2.3 CONTROL OF MATERIALS Page 1

OPEN PART

3.2.S.2.3.2 STARTING MATERIAL
(3S)-Benzyl1,2,3,4-tetrahydroisoquinoline-3-carboxylate p-toluene sulfonate salt
(QN II) is first converted to the base benzyl 1,2,3,4-tetrahydroisoquinoline-3-
carboxylate which is extracted in toluene. The base then undergoes condensation
reaction with ethoxy carbonylphenylpropyl alanine (ECPP–alanine).
Therefore (3S)-Benzyl1,2,3,4-tetrahydroisoquinoline-3-carboxylate p-toluene

sulfonate salt known as QN II and ethoxy carbonylphenylpropyl alanine (ECPP–
alanine) known as S1-compound are used as starting materials.
Sr. Name of starting Name & address of manufacturer/ approved

No. material source
Aarti Industries Limited.
Custom Synthesis Division
Plot No. 22-C/1,Ist Phase, GIDC Estate,
1 QN-II Vapi - 396 195
Dist. Valsad, Gujarat, India.
FEI number: 3007850324
DUNS number: 650790228
Zhejiang Changming Pharmaceutical Co.,
Ltd.
2 S-1 compound
Add. Potang Industrial Park, Tiantai, Zhejiang,
China.
The vendor information of starting materials is given in Restricted Part.

OPEN PART

Lithium is used in the manufacturing process of starting material S-1 compound.
The content of Lithium is checked in starting material S-1 compound. The results
are as follows.
Lithium content in S-1 compound batches:
Sr. No. S-1 compound Batch No. Lithium content

1 3001-1605-083 0.2402 ppm
2 3001-1605-082 0.5746 ppm
3 3001-1605-077 1.034 ppm
Reports of the same are provided on page no. 4 to 9.
As per ICH Q3D guideline for elemental impurities, Lithium is class 3 elemental
impurity and the results above shows that the content of Lithium is much less
than the 30% of the ICH limit for Lithium (55 ppm).
Quality equivalence data for Quinapril hydrochloride USP manufactured by using

both routes of synthesis of starting material S-1 compound is provided on page
no. 10 to 17.
Content of S,R-isomer in starting material ECPPA (S1-compound):
We have studied the presence of S,R-isomer in 3 batches of starting material

ECPPA (S1-compound) and found to be below detectable limit. The batch
analysis results are as tabulated below:
Batch Number Content of S,R-isomer Limit

3001-1802-026 Below Detection Limit
3001-1802-027 Below Detection Limit Not More Than 0.20%
3001-1802-028 Below Detection Limit
We have suitably verified this in-house HPLC method and the limit of detection
(LOD) and limit of quantification (LOQ) is as tabulated below. The specificity &
selectivity, limit of detection, limit of quantification, precision at LOQ, accuracy
at LOA and linearity & range have been determined.
LOD LOQ
Impurity
In ppm In % w.r.t. sample In ppm In % w.r.t. sample
S,R-isomer 0.000414 0.021 0.000828 0.041
The method verification report is provided in section 3.2.S.4.3 of section

3.2.S.4.3.

FDA
~~~~\
COA: Centre of Excellence

(A Division of Vapi Green Enviro Limited)
Approved
Laboratory
\fr{~MJ).J)
~~~-
Certificate
No.T-3159
CENTRE OF EXCELLENCE
Quality Testing Facility & R&D Centre CIN No.: U74210GJ1997GAP031525
CERTIFICATE OF ANALYSIS
~J)
Certificate No. . COE/07 414/R&D/16-17 Date :20/10/2016
~
IP~~
Inward No. 7515 Date : 13/10/2016
u
~~
QJ
Sponser Name . Aarti Industries Limited (Unit- IV)
~.-.,
o~.J
~~
Address . Plot No: E-50 MIDC, Tarapur, Tal: Palghar
("-~
,~"1 Thane- 401506
(;')
(.) SAMPLE DETAILS
Sample Name .. S1 Compound
Batch No. . 3001 -1605- 083 Sample Qty. :
MFG. Date . NIM Exp. Date : N/M
Description Powder Sample
ANALYSIS RESULT
Sr. No. Parameter Result
Lithium (Li) Content by ICP 0.2402 ppm
Note : Party asked for above test only
The above test certificate is issued by the C.O.E. on basis of the sample qty received in lab for analysis. The Test Report can not be
reproduced completly or part, in any form of media (Including Print) Without explicit written permission from management of Centre of
Excellence.
~ I
.,1 I~
Analysed By Checked By Autl~prised By
Survey No. 863/P, 864, 735/P, Phase I, Near GIDC Water Filtration Plant, GIDC, Vapi- 396 195. Dist. Valsad, Gujarat.

CENTRE OF EXCELLENCE 10/18/2016
Mean Data
ID: BLANK Seq. No.: 1 AIS Pos:
Sample Qty g Prep. Vol.: Dilution: Date: 2016/10/18 11:14:13

Analyte Corr. Intensity Cone (Calib) Std. Dev. Calib Units Cone (Sample) Std. Dev. Sample Units RSD
Li 670.784 9,253.2 [0.00] 207.91 mg/L 2.25%
Mean Data
ID: STDO.l PPM Seq. No.: 2 AIS Pos: 2

Li 670.784 3,230,540.8 [0.1] 22,059.96 mg/L 0.68%
Mean Data
ID: STD l.OPPM Seq. No.: 3 AIS Pos: 3
Sample Qty g . Prep. Vol.: Dilution: Date: 2016/10/18 11:31:28

Li 670.784 37,519,722.5 [1.0] 103,187.38 mg/L 0.28%
Mean Data
ID: STD2.0PPM Seq. No.: 4 AIS Pos: 4
Sample Qty g .Prep. Vol.: Dilution: Date: 2016/10/18 11:37:49

Li 670.784 83,496,093.9 [2.0] 53,911.73 mg/L 0.06%
Mean Data
ID: REAGENT BLANK-I Seq. No.: 5 AIS Pos: 5
Sample Qty g Prep. Vol •.: .. Dilution: Date: 2016/10/18 11:47:45

Li 670.784 3,601.4 0.0001 0.00001 mg/L 0.0001 0.00001 mg/L 13.40%
Mean Data
ID: 3001 -1605 -083 Seq. No.: 16 AIS Pos:
Sample Qty 1.03 g Prep. Vol.: 20.00 Dilution: Date: 2016/10/18 12:17:01
Li 670.784 511,538.6 0.0124 0.00016 mg/L 0.2402 0.00308 ppm 1.28%
~By 1
~Checked By

FDA
COA: Centre of Excellence

(A Division of Vapi Green Enviro Limited)
Approved
Laboratory
Certificate
No.T-3159
Certificate No. CO E/07 413/R&D/16-17 Date :20/10/2016
Inward No. 7514 Date : 13/10/2016
Sponser Name Aarti Industries Limited (Unit- IV)
Address Plot No: E-50 MIDC, Tarapur, Tal: Palghar
Thane - 401506
SAMPLE DETAILS
Sample Name S1 Compound
Batch No. 3001- 1605- 082 Sample Qty. :
MFG. Date NIM Exp. Date : N/M
Description Powder Sample
ANALYSIS RESULT
Note :Party asked for above test only
Excellence.
;::> c
Analysed By Checked By
Survey No. S63/P, 864, 735/P, Phase I, Near GIDC Water Filtration Plant, GIDC, Vapi- 396 195. Dist. Valsad, Gujarat.
- - ... - -

Mean Data
D: BLANK Seq. No.: A/S Pos:
)ample Qty g Prep. Vol.: Dilution: Date: 2016/10/18 11:14:13

~nalyte Corr. Intensity Cone (Calib) Std. Dev. Calib Units Cone (Sample) Std. Dev. Sample Units RSD
_j 670.784 9,253.2 [0.00] 207.91 mg/L 2.25%
Mean Data
D: STD 0.1 PPM Seq. No.: 2 AIS Pos: 2
;ample Qty g Prep. Vol.: Dilution: Date: 2016/10/18 11:23:45

_j 670.784 3,230,540.8 [0.1] 22,059.96 mg/L 0.68%
Mean Data
iample Qty g Prep. Vol.: Dilution: Date: 2016/10/18 11:31:28

j 670.784 37,519,722.5 [1.0] 103,187.38 mg/L 0.28%
Mean Data
iample Qty g Prep. Vol.: Dilution: Date: 2016110/18 11:37:49

j 670.784 83,496,093.9 [2.0] 53,911.73 mg/L 0.06%
Mean Data
D: REAGENT BLANK-I Seq. No.: 5 AIS Pos: 5
iample Qty g Prep. Vol.: Dilution: Date: 2016/10/18 11:47:45

j 670.784 3,601.4 0.0001 0.00001 mg/L 0.0001 0.00001 mg/L 13.40%
\t1ean Data
): 3001 -1605 -082 Seq. No.: 15 AIS Pos:
lample Qty 1.03 g Prep. Vol.: 20.00 Dilution: Date: 2016/10/18 12:14:05
j 670.784 1,211,023.5 0.0295 0.00030 mg/L 0.5746 0.00575 ppm 1.00%
(t]:,;"'
1 ~eked By

FDA
COJ: Centre of Excellence (A Division of Vapi Green Enviro Limited)

Approved
Laboratory
$(.1)
~~~4+
:~-
Certificate
No,T-3159
Certificate No. . COE/07 412/R&D/16-17 Date :20/10/2016
Inward No. . 7513 Date : 13/10/2016
Sponser Name Aarti Industries Limited (Unit- IV)
Address Plot No: E-50 MIDC, Tarapur, Tal: Palghar
Thane - 401506
SAMPLE DETAILS
Sample Name S1 Compound
Batch No. 3001- 1605- 077 Sample Qty. :
MFG. Date .. NIM Exp. Date : N/M
Description .. Powder Sample
ANALYSIS RESULT
Note : Party asked for above test only
Excellence.
liN._.
Analysed By Checked By Autl~rised By
Survey No. 863/P, 864, 735/P, Phase I, Near GIDC Water Filtration Plant, GIDC, Vapi- 396 195. Dist. Valsad, Gujarat.
• "1 • I" " 0
n L _____ /I"\t""\fA."\I"'\A11~r\.,.., r\.,_,1AI"\£'\,_,I"\/O II '"1:T1 "J

Mean Data
ID: BLANK Seq. No.: AIS Pos:

Li 670.784 9,253.2 [0.00] 207.91 mg/L 2.25%
Mean Data
ID: STD 0.1 PPM Seq. No.: 2 AIS Pos: 2

Li 670.784 3,230,540.8 [0.1] 22,059.96 mg/L 0.68%
Mean Data
ID: STD 1.0 PPM Seq. No.: 3 AIS Pos: 3

Li 670.784 37,519,722.5 [1.0] 103,187.38 mg/L 0.28%
Mean Data
ID: STD2.0PPM Seq. No.: 4 AIS Pos: 4

"nalyte Corr. Intensity Cone (Calib) Std. Dev. Calib Units Cone (Sample) Std. Dev. Sample Units RSD
Li 670.784 83,496,093.9 [2.0] 53,911.73 mg/L 0.06%
Mean Data
D: REAGENT BLANK-I Seq. No.: 5 AIS Pos: 5
)ample Qty g Prep. Vol.: Dilution: Date: 2016/10/18 11:47:45

u 670.784 3,601.4 0.0001 0.00001 mg/L 0.0001 0.00001 mg/L 13.40%
Mean Data
D: 3001 -1605 -077 Seq. No.: 13 AIS Pos:
)ample Qty 1.00 g Prep. Vol.: 20.00 Dilution: Date: 2016/10/18 12:10:07
~i 670.784 2,109,657.2 0.0515 0.00032 mg/L 1.034 0.0064 ppm 0.62%
~}J ~
"rti:Wsed By 1 Weked By

QUALITY COMPARISON DATA

RESULTS
Sr.
TESTS Before change After Change SPECIFICATION
No.
QN-13005 QN-13006 QN-13007 QN-16033 QN-16034 QN-16035
1. Description White White White White White White A white to off-white powder, with
powder powder powder powder powder powder pink cast at times.
2. Solubility Complies Complies Complies Complies Complies Complies Freely soluble in water.
3. Identification The Infrared spectrum of sample
A) By IR Spectrum Complies Complies Complies Complies Complies Complies should be concordant with that of
Quinapril HCl Working Standard.
The retention time of the major
peak in the chromatogram of
assay preparation should be
B) By HPLC Complies Complies Complies Complies Complies Complies
correspond to the chromatogram
of the standard preparation, as
obtained in the assay.
4. Specific optical Between +14.4° and +15.4° at
+15.08° +15.15° +15.16° +15.12° +15.10° +14.93°
rotation (SOR) 25°C on anhydrous basis.
5. Water content 0.66% w/w 0.76% w/w 0.68% w/w 0.86% w/w 0.81% w/w 0.83% w/w Not more than 1.0% w/w
6. Residue on Ignition 0.04% w/w 0.04% w/w 0.04% w/w 0.06% w/w 0.03% w/w 0.08% w/w Not more than 0.1% w/w
7. Heavy metal Complies Complies Complies Complies Complies Complies Not more than 0.002%
8. Limit of Residual solvents (By HSGC)
Acetone Not detected Not detected Not detected Not detected Not detected 7 ppm NMT 2000 ppm
Acetonitrile 91 ppm 79 ppm 84 ppm 13 ppm 13 ppm 19 ppm NMT 410 ppm
Di-isopropyl ether Not detected Not detected Not detected Not
2 ppm 2 ppm NMT 700 ppm
detected
Ethyl acetate 1913 ppm 1959 ppm 1877 ppm 272 ppm 23 ppm 8 ppm NMT 3000 ppm
Toluene Not detected Not detected Not detected 8 ppm Not detected 4 ppm NMT 890 ppm

RESULTS
Sr.
TESTS Before change After Change SPECIFICATION
No.
QN-13005 QN-13006 QN-13007 QN-16033 QN-16034 QN-16035
9. Related Compounds (By HPLC)
Related compound A 0.21% 0.20% 0.21% 0.19% 0.18% 0.23% NMT 0.5%
Related compound B 0.18% 0.18% 0.18% 0.03% 0.03% 0.05% NMT 0.5%
Any unknown
0.07% 0.07% 0.07% 0.04% 0.04% 0.07% NMT 0.10%
impurity
Total impurities 0.63% 0.60% 0.61% 0.32% 0.30% 0.45% NMT 2.0%
10. Content of Chloride Not less than 7.2% and Not more
7.48% 7.23% 7.31% 7.46% 7.41% 7.31%
(By potentiometry) than 7.6%
11. Assay (By HPLC) Not less than 98.5% and Not
99.18% 99.48% 99.88% 99.24% 99.54% 100.07% more than 101.5% on anhydrous
basis.
12 Additional Test
Limit of palladium 0.32 ppm 0.37 ppm 0.39 ppm 2 ppm 2 ppm 2 ppm Not more than 0.001% (10 ppm)
ND: Not detected

NLT: Not less than
NMT: Not more than

----------~~~~ma~~ Factory : Unit - IV, Plot No. E-50, MIDC, Tarapur,
Taluka & District- Palghar, Pin- 401 506. Maharashtra, INDIA.
Tel. No. : (02525) 645001, 645452, Telefax : (02525) 661092
Batch No. : QN-16033 Date of Mfg. : JUL-2016
A.R. No. : FG/0392/16 Date ofExp. : JUN-2021
Batch Qty. : 86.50 Kg. Date of Release : 19/08/16
Sr.# TESTS RESULTS SPECIFICATION

1. Description White powder A white to off-white powder, with pink cast
at times.
2. Solubility Complies Freely Soluble in water.
3. Identification The Infrared spectrum of sample should be
Complies concordant with that of Quinapril
a) By IRSpectrum Hydrochloride Working Standard.
b)ByHPLC Complies The retention time of the major peak in the
chromatogram of assay preparation should be
correspond to the chromatogram of the
standard preparation, as obtained in the assay.
4. Specific Optical +15.12° Between+ 14.4° and+ 15.4° at 25°C on
Rotation anh_ydrous basis.
5. Water Content (By KF) 0.86%w/w Not more than 1.0% w/w
6. Residue on Ignition 0.06%w/w Not more than 0.1% w/w
7. Heavy Metal Complies Not more than 0.002%
8. Content of Chloride 7.46% Not less than 7.2% and Not more than 7.6%
(By potentiometry )
9. Related Compounds 0.19% Related Compound A :NMT-0.5%
(ByHPLC) 0.03% Related Compound B :NMT-0.5%
0.04% Any unknown impurity :NMT-0.10%
0.32% Total impurities :NMT-2.0%
10. Assay 99.24% Not less than 98.5% and Not more than
(ByHPLC) 101.5% on anhydrous basis.
11. Residual solvents Not Detected Acetone NMT 2000 ppm
(ByHSGC) 13 ppm Acetonitrile NMT 41 0 ppm
2ppm Di-isopropyl ether NMT 700 ppm
272 ppm Ethyl Acetate NMT 3000 ppm
8ppm Toluene NMT 890 ppm
Additional Test
Palladium content 2ppm Not more than 0.001% (10 ppm)
. 1comp.r1es as per USP and ab ove spec1"fi1catwn
R emark : The matena
Analyst Checked By Approved By
RD ~tutlt
Head Quality Control
~b
Head Quality Assurance
Note: Methylene chloride is not used in the manufacturing process.
Precaution: Do the handling of material under nitrogen gas because it is highly hygroscopic in nature.
Storage: Store at t~mperature between 2- 8 o C
HEAD-OFFICE :
71, Udyog Kshetra, 2nd Floor, Mulun(:l Goregaon Link Road, Mulund (W), Mumbai - 400 080. INDIA
Tel. : 00- 91 - 22- 67976666, 67976697, 25918195 • Fax: 00- 91 - 22- 25904806, 25653185/ 3234
Regd. Office
January, 2020: Plot No. 801/23, G.I.D.C.
3.2.S.2.3Estate,
CONTROL III,MATERIALS
Phase-OF Vapi- 396195, Dist. Valsad, Gujrat, INDIA
Page 15
Website: www.aartigroup.com • CIN- L24110GJ1984PLC007301
(il AA.RTC CNOUSTRCES UMCTEO
---------------------------------------------Factory : Unit- IV, Plot No. E-50, MIDC, Tarapur,
Taluka & District- Palghar, Pin - 401 506. Maharashtra, INDIA.
Tel. No.: (02525) 645001, 645452, Telefax: (02525) 661092
A.R. No. : FG/0396/16 Date ofExp. : JUN-2021

at times.
3. Identification The Infrared spectrum of sample should be
a) By IR Spectrum Hydrochloride Working Standard.
b)ByHPLC Complies The retention time of the major peak in the
Rotation anhydrous basis.
5. Water Content (By KF) 0.81% w/w Not more than 1.0% w/w
(By potentiometry )
(ByHPLC) 10 1.5% on anhydrous basis.
11. Residual solvents Not Detected Acetone NMT 2000 ppm
(ByHSGC) 13 ppm Acetonitrile NMT 410 ppm
2ppm Di-isopropyl ether NMT 700 ppm
23 ppni Ethyl Acetate NMT 3000 ppm
Not Detected Toluene NMT 890 ppm
Additional Test
Palladium content Not more than 0.001% (10 ppm)
Anal st Checked B A
RD
Head Quali Control
Storage: Store at temperature between 2- 8 o· c
HEAD·OFFICE :
71, Udyog Kshetra, 2nd Floor, Mulunq Goregaon Link Road, Mulund (W), Mumbai - 400 080. INDIA
Tel. : 00- 91 - 22- 67976666, 67976697, 25918195 • Fax: 00- 91 - 22- 25904806, 25653185/ 3234
Regd. Office
3.2.S.2.3Estate,
CONTROLPhase-
OFIII,MATERIALS
Vapi- 396195, Dist. Valsad, Gujrat, INDIA
Page 16
(il
---------------------------------------------
AART( (NOUSTR(ES UM(TEO
Factory : Unit - IV, Plot No. E-50, Mlf?C, Tarapur,
Taluka & District- Palghar, Pin - 401 506. Maharashtra, INDIA.
Tel. No. : (02525) 645001, 645452, Telefax : (02525), 661092
Batch No. : QN-16035 Date of Mfg. : AUG-2016
A.R. No. : FG/0426/16 Date ofExp. : JUL-2021

at times.
3. Identification The InfrCl;red spectrum of sample should be
a) By IR Spectrum Hydrochloride Working Standard.
b) ByHPLC Complies The retention time of the major peak in the
Rotation anhydrous basis.
5. Water Content (By KF) 0.83 %w/w Not more than 1.0% w/w
(By potentiometry )
(By HPLC) 101.5% on anhydrous basis.
11. Residual solvents 7ppm Acetone NMT 2000 ppm
(ByHSGC) 19ppm Acetonitrile NMT 410 ppm
~
Not Detected Di-isopropyl ether NMT 700 ppm
8ppm Ethyl Acetate NMT 3000 ppm
4ppm Toluene NMT 890 ppm
Additional Test
Palladium content Not more than 0.001% (10 ppm)
Checked B
CP
~"'''
Head Quali Control
Storage: Store at temperature between 2- 8 o C
HEAD·OFFICE :
71, Udyog Kshetra, 2nd Floor, Mulun~ Goregaon Link Road, Mulund (W), Mumbai - 400 080. INDIA
Tel. : 00- 91 - 22- 67976666, 67976697, 25918195 • Fax: 00- 91 - 22- 25904806, 25653185/ 3234
Regd. Office
3.2.S.2.3Estate,
CONTROLPhase-
OFIII,MATERIALS
Vapi- 396195, Dist. Valsad, Gujrat, INDIA
Page 17
OPEN PART

3.2.S.2.4 CONTROL OF CRITICAL STEPS AND INTERMEDIATES
3.2.S.2.4.1 CRITICAL PROCESS STEPS

Critical process steps have been given along with the detailed manufacturing
process - refer section 3.2.S.2.2. The same are also reproduced in section
3.2.S.2.4 of Restricted Part.
3.2.S.2.4.2 IN-PROCESS TESTS
Testing procedure for in-process analysis is given in section 3.2.S.2.4 of

Restricted Part.
3.2.S.2.4.3 INTERMEDIATES:
Benzyl Quinapril Maleate is an intermediate in the manufacturing process of

Quinapril HCl.
Sr. No. Name of Intermediate Test Procedure Rev. No.

1 Benzyl Quinapril Maleate (QN-III) AQC/ST/IT/039 01
Testing procedure for intermediate is provided in Restricted Part.
January, 2020 3.2.S.2.4 CONTROL OF CRITICAL STEPS Page 1

AND INTERMEDIATES
OPEN PART

3.2.S.2.5 PROCESS VALIDATION AND/OR EVALUATION
Process validation report QA/PV/R/QN-I/001/Rev 03 with batch size 120 kg is
provided in Restricted Part.

Process validation report QA/PV/R/QN/001 Rev 07 is given in Restricted Part.
January, 2020 3.2.S.2.5 PROCESS VALIDATION AND/OR EVALUATION Page 1

OPEN PART

3.2.S.2.6 MANUFACTURING PROCESS DEVELOPMENT
Detailed discussion on manufacturing process development is provided in section

3.2.S.2.6 of Restricted Part.
January, 2020 3.2.S.2.6 MANUFACTURING PROCESS DEVELPOMENT Page 1

OPEN PART

3.2.S.3
CHARACTERISATION
January, 2020 3.2.S.3 CHARACTERISATION Page 1

OPEN PART

3.2.S.3.1 ELUCIDATION OF STRUCTURE AND OTHER CHARACTERISTICS
ELUCIDATION OF STRUCTURE
Quinapril hydrochloride is a well-established and characterized drug. The

confirmation about its structure was obtained by the following.
PHYSICO – CHEMICAL TESTS:

Following are physico – chemical tests as per USP providing confirmation about
the structure of Quinapril hydrochloride.
1 IDENTIFICATION
A. The specific optical rotation as per USP, observed was + 14.57 to +14.77
(Limit +14.4 to +15.4), calculated with reference to the dried substance.
B. IR spectrum:
The IR spectrum of the Quinapril HCl AH/0504/28/WS was recorded on
FTIR 8400 Shimadzu make. The functional group assignments resemble that
of Quinapril.
FUNCTIONAL GROUP ASSIGNMENT – IR SPECTRUM
Sr. No. Wave no. Cm –1 Assignment

1. 1649 Secondary amine - NH-
2. 1741.6, 1205.4 Acyclic ester -COOC2H5 C=O and C-O-
3. 3024.2 -OH of carboxylic acid -COOH-
The IR spectrum is given on page no 2.
January, 2020 3.2. S.3.1 ELUCIDATION OF STRUCTURE AND Page 1

OTHER CHARACTERISTICS
January, 2020 3.2.S.3.1 ELUCIDATION OF STRUCTURE AND Page 2
OPEN PART

2 SOLUBILITY:
Solubility profile matched with that given in the monograph viz., freely
soluble in aqueous solutions.
3 UV SPECTRUM
The UV spectrum of a 50 ppm solution of Quinapril HCl AH/0504/28/WS
was recorded using UV-Vis Spectrophotometer model no – UV 1601,
Shimadzu make. It exhibited maxima at about 205 nm.
The UV-spectrum is given on page no 4 to 5.

OPEN PART

4 NMR
COOH
H3C O O
CH3
N
N .HCl
H
O
NMR spectrum of Quinapril Hydrochloride batch number AH/0504/28/WS was

recorded on Bruker AC 200 model and solution of the sample in deuterated
water.
The NMR structural interpretation is given below.
Sr. No. Chemical Shift (δ) ppm Assignment

1. 0.99 to 1.02 Triplet for Ester methyl group
2. 2.62 to 2.64 Doublet for –NH- group proton
3. 3.96 to 4.03 Multiplet for CH3-CH2-O-CO- group
4. 4.29 to 4.33 Triplet for benzylic –CH2- group
5. 6.87 to 7.19 Multiplet for aromatic protons
The NMR spectrum is given on page no 7.

OPEN PART

5 MASS SPECTRUM
The Mass Spectrum of Quinapril Hydrochloride QN/0504/28/WS was recorded
on Waters Macromass Quattro MicroTM API.
The molecular ion [M+H]+ was detected at (m/e 439.42) which corresponds to a
molecular weight of 438 of Quinapril base.
The mass spectrum of the Quinapril hydrochloride Batch number
QN/0504/28/WS given on page no 9.

OPEN PART

6. ELEMENTAL ANALYSIS
C, H, N and O (Elemental analysis of Quinapril hydrochloride Batch number
QN/0504/28/WS was carried out on instrument make Thermoquest and Model
Flash EA Series (Eager 300).
The following table gives the comparison between the theoretical % of C, H, N
and O and the actually obtained % in the sample.
Elements Theoretical Value Actual Value

C 63.22 % 63.32 %
H 6.58 % 6.81 %
N 5.90 % 5.72 %
O 16.84 % 16.73 %
The above elemental analysis correlates well with the theoretical values thus
confirming the structure.
The elemental analysis report is given on page no. 11 to 13.

OPEN PART

Isomerism : There are 3 chiral centers.

Polymorphism : The X-ray diffraction pattern was determined for three
validation batches and they were found to be completely
concordant. Thus, it could be concluded that the same
amorphous form is produced in the production batches.
The XRD spectra are given on following pages.
Chirality : Quinapril Hydrochloride has three chiral centers. The
specific optical rotation is + 14.4° to + 15.4° at 25C.

*** Basic Data Process ***
Group Name Quinapril HCL

Data Name 21L007 02
FiIe Name 21L001 02.RAW
Sample Name QN-07001 (cM)
Comment QN-07001 (cM)
Data fnfomation
Data Name 27L007 02
File Name 27]-001 02.RAW
Sample Name QN-07001 (cM)
Comment, QN-07001 (CM)
Date & Time L0-28-07 00:22233
Measurement Condition
X-ray tube
target
voltage 40.0 (kv)
current 30.0 (mA)
Slits
divergence slit 1.00 (deg)
scatter slit 1.00 (deS)
receivinq sl_it 0. 15 (mm)
Scanning
drive axis Theta-2Theta
scan range 5.0000 - 40.0000 (deg)
scan mode Continuous Scan
scan speed 2.0000 (deg/nin)
sampling pitch 0.0500 (deg)
preset time 1.50 (sec)
Beta Axis
Oscillation Ranqe 0.0000 - 350.0000 (des)
Data Process Condition
Smoothing AUTO ]
smoothing points 0
B. G.Subtraction AUTO ]
sampling points 0
repeat times 0
KaL-a2 Separate MANUAL ]
KaL a2 ratio s0 (?)
Peak Search AUTO ]
differential points 0
F W H Mt h r e s h o l d 0.000 (deS)
intensity threshold 0 (par mil-)
F W H Mr a t i o (n-1) /n 0
System error Correction NOI
Precise peak Correction NOI

Page 16
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Data Name 271,001
FiIe Name 2 7 1 0 0 7 .R A W
Sample Name Q N - 0 70 0 3
Comment QN-07003
*** Basic Data PTOCeSS ***
Data fnfomation
Group Name Quinapril- HCL
Data Name 2 7L 0 0 7
File Name 2 7 1 0 0 7 .R A W
Sample Name QN-07003
Comlnent QN-07003
Date & Time 70-28-07 00: 02:15
Measurement Condi_tion
X-ray tube
target Cu
voltage 40. 0 (kv)
currenc 30. 0 (mA)
SIits
divergence slit 1.00 (deS)
scatter slit 1.00 (deg)
receiving slit 0.15 (run)
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scan range s.0000 - 40. 0000 (des)
scan speed 2.0000 (deg/min)
sampling pitch 0.0500 (deg)
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OPEN PART

3.2.S.3.2 IMPURITIES
The impurities in the drug substances have been categorized in to three main
categories (Ref.: Impurities in New Drug Substances - Q3A (R) – ICH
Guidelines, dated 7th Feb., 2002):
1. Organic Impurities
2. Inorganic Impurities
3. Solvents
ORGANIC IMPURITIES:
The Organic Impurities could arise due to:
1. Starting material & raw materials.

2. Intermediates
3. Process impurities i.e. by-products / degradation products
4. Reagents, ligands and catalysts
STARTING MATERIAL & RAW MATERIALS

The starting material and raw materials, which could be the source of impurities
in Quinapril HCL are:
STARTING MATERIAL:
(S)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid phenyl methyl ester p-
toluene sulfonate – QN – II
Ethoxy carbonyl phenyl propyl alanine (ECPP alanine) – S1 compound.
RAW MATERIALS:
NBS – 1-hydroxy benzotriazole
Di-cyclohexyl carbodiimide
January, 2020 3.2.S.3.2 IMPURITIES Page 1

OPEN PART

STARTING MATERIAL:
QN – II.
SO3H
O O
HN .
CH3
(S)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid phenyl methyl ester p-

toluene sulfonate
Formation:
This compound is a starting material for Quinapril synthesis.

It can be detected by the HPLC procedure for related substances for Quinapril as
per USP. Its RRT is at about 0.46.

OPEN PART

Ethoxy carbonyl phenyl propyl alanine (ECPP Alanine)
H
N COOH
O H H
CH3
H3C O
(S)-2-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]propanoic acid
Formation:
This impurity is the starting material. It gets removed during the manufacturing
process as it soluble in ethyl acetate and it also gets removed with sodium
bicarbonate washing.

OPEN PART

RAW MATERIALS:
NBS - 1- Hydroxybenzotriazole.
N
N
N
OH
Molecular formula = C6H5N3O
Molecular weight = 135.13
It is used as a coupling agent. It is highly soluble in the basic media and gets
removed during washing with NaHCO3.
It is soluble in ethyl acetate, hence if present; it gets removed during washing
with ethyl acetate.

OPEN PART

Di-cyclohexyl carbodiimide: Di-cyclohexyl urea:
O
N C N N C N
H H
Molecular formula = C13H22N2 Molecular formula = C13H24N2O

Molecular weight = 206.33 Molecular weight = 224.35
Formation:
Di-cyclohexyl carbodiimide is used as dehydrating agent. During reaction it gets

converted to di-cyclohexyl urea. Urea is totally insoluble in toluene. After the
reaction the toluene layer is filtered and given the requisite work up procedure by
which the urea gets completely removed.

OPEN PART

QN - III
O
O
O O
COOH
N .
N
H COOH
O
(S,S,S)-2-[[2–[1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxo propyl]-1,2,3-
tetrahydro–3-isoquinolinecarboxylic acid phenyl methyl ester maleate

OPEN PART

QN - IV
O
O
O O
N
N
H
O
(S,S,S)-2-[[2–[1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-1oxopropyl]-1,2,3,4-
tetrahydro–3-isoquinolinecarboxylic acid phenyl methyl ester

OPEN PART

PROCESS RELATED IMPURITY
BY-PRODUCTS/ DEGRADATION PRODUCTS):
Following process related impurities – related compounds have been specified in
the USP.
IMPURITY A
O O
O
N
N
O
Molecular Weight = 420.51

Molecular Formula = C25H28N2O4
2-(3-Methyl-1,4-dioxo-1,3,4,6,11,11a-hexahydro-pyrazino[1,2-b]isoquinolin-2-
yl)-4-phenyl-butyric acid ethyl ester (Quinapril di-keto piperazine)
Formation:
This impurity may form during the synthesis of Quinapril due to the cyclization
resulting in the formation piperazine ring especially at high temperature. During
storage at high temperature, slowly this impurity emerges as evident from the
accelerated stability studies at 40±2C and 75±5% RH. This impurity is either
absent or its concentration is below 0.5% in Quinapril Hydrochloride.

OPEN PART

IMPURITY B
OH
O
HO O
N
N
H
O
Molecular Weight = 410.47

Molecular Formula = C23H26N2O5
(S,S,S)-2-[2-(1-Carboxy-3-phenylpropylamino)-propionyl]-1,2,3,4-tetrahydro-
isoquinoline-3-carboxylic acid (Quinapril diacid)
Formation:
This impurity may form during the synthesis of Quinapril under highly acidic or
alkaline conditions due to the hydrolysis of Quinapril. Since the conditions
employed are mild, the possibility of formation of this impurity is at minimum
level.
This impurity is either absent or its concentration is below 0.5% in Quinapril.

OPEN PART

Following table lists all impurities in Quinapril HCL in 3 validation batches
TABLE – 1.
Tests Results (in %)
Limit (%)
Validation Batch No. QN-17020 QN-17022 QN-17023
Related substances (By HPLC)
Related compound A 0.13 % 0.19 % 0. 13 % NMT : 0.5 %
Related compound B 0.05 % 0.05 % 0.03 % NMT : 0.5 %
Any unknown impurity 0.06% 0.08 % 0.06 % NMT : 0.10 %
Total impurities 0.31 % 0 .39% 0.27 % NMT : 2.0 %
The above table indicates that the impurities are very well controlled.
HPLC/GC chromatograms pertaining to batch number QN-17020 is provided in
Restricted Part.

OPEN PART

REAGENTS, LIGANDS AND CATALYSTS

Following Table gives the results of 3 validation batches.
Reagents, Ligands and Catalysts
Validation Batch No. QN-17020 QN-17022 QN-17023 Limit
Residue on Ignition 0.05 % 0.06 % 0.05 % NMT 0.1% w/w
Palladium content 4.10 ppm 3 ppm 4 ppm NMT 10 ppm
Lithium is used in the manufacturing process of starting material S-1 compound.

The content of Lithium is checked in starting material S-1 compound. The results
are as follows.
Lithium content in S-1 compound batches:
Sr. No. S-1 compound Batch No. Lithium content

1 3001-1605-083 0.2402 ppm
2 3001-1605-082 0.5746 ppm
3 3001-1605-077 1.034 ppm
Kindly refer page no. 145 to 150 of section 3.2.S.2.3 for analysis report.
As per ICH Q3D guideline for elemental impurities, Lithium is class 3 elemental
impurity and the results above shows that the content of Lithium is much less
than the 30% of the ICH limit for Lithium (55 ppm).
RISK ASSESSMENT /EVALUATION OF ELEMENTAL

IMPURITIES:
The following elements are considered (intentionally and/or not intentionally

added) for risk assessment as per ICH/EU/US regulations.
Element Class Remark

Cadmium (Cd) 1 Not intentionally added
Lead (Pb) 1 Not intentionally added
Arsenic (As) 1 Not intentionally added
Mercury (Hg) 1 Not intentionally added
Cobalt (Co) 2A Not intentionally added
Vanadium (V) 2A Not intentionally added
Nickel (Ni) 2A Not intentionally added
Palladium(Pd) 2B Intentionally added
Lithium 3 Intentionally added

OPEN PART

With reference to ICH/EU/US regulations on elemental impurities, PDEs
values for oral, parenteral and inhalation routes of administration are
available.
Oral PDE
Element Class
μg/day
Cadmium (Cd) 1 5
Lead (Pb) 1 5
Arsenic (As) 1 15
Mercury (Hg) 1 30
Cobalt (Co) 2A 50
Vanadium (V) 2A 100
Nickel (Ni) 2A 200
Palladium(Pd) 2B 100
Lithium 3 550
Based on ICH-Q3D (option 1), the common permitted concentration of each

element is determined using equation-1 and the actual maximum daily intake
of drug substance with oral concentration of each element is considered for
an evaluation.
We have considered oral PDE value for Quinapril Hydrochloride as it is used

for oral, hence above listed elements and concentration is calculated
considering the maximum daily dose (MDD) of Quinapril Hydrochloride as
Concentration (g/g) = PDE (g/day) /10
The calculated concentrations (μg/day or ppm) using above equation is as

below:
Oral PDE in Calculated concentration
Element Class
µg/day based on MDD in μg/day
Cadmium (Cd) 1 5 0.5
Lead (Pb) 1 5 0.5
Arsenic (As) 1 15 1.5
Mercury (Hg) 1 30 3
Cobalt (Co) 2A 50 5
Vanadium (V) 2A 100 10
Nickel (Ni) 2A 200 20
Palladium(Pd) 2B 100 10
Lithium 3 550 55

OPEN PART

Aarti Industries Limited has verified and confirmed that the carryover
/presence of Cd, Pb, As, Hg, Co, V, Ni, Pd and Li in three commercial
batches of Quinapril Hydrochloride and the results are as tabulated below and
the analysis report is provided on page no. 423 to 617 in validation section
3.2.S.4.3.
Results
Elements
QN-17020 QN-17021 QN-17022
Cadmium (Cd) 0.0001 0.0006 0.0003
Lead (Pb) 0.0050 0.0213 0.0048
Arsenic (As) 0.0047 0.0060 0.0059
Mercury (Hg) ND ND ND
Cobalt (Co) 0.0070 0.0089 0.0138
Vanadium (V) 0.0132 0.0196 0.0191
Nickel (Ni) 2.4587 3.4032 5.3397
Palladium(Pd) 0.0036 0.0111 0.0068
Lithium (Li) 0.0917 0.0911 0.0611
Thus, the above evaluation data confirmed that, the elemental impurities are
well controlled in the manufacturing process.
The intentionally added catalyst palladium and Lithium (Starting material) is also
controlled in the final drug substance by the test for Palladium content by ICP-
MS with an in-house limit of NMT 5 ppm (i.e. 0.0005%).

OPEN PART

RESIDUAL SOLVENTS AND ORGANIC VOLATILE IMPURITIES:
Class 1 solvent: No class 1 solvent is used in the manufacturing process of
Quinapril hydrochloride.
The solvents used in the manufacturing process are acetone, acetonitrile,

toluene, ethyl acetate and di-isopropyl ether (DIPE). Following table gives
their classification as well as their limit:
List of solvents used in the manufacturing of quinapril hydrochloride along with

ICH & internal limits
Sr. ICH Limit Internal

No. Solvent Stage Class
ppm Limit ppm
Starting material,
1 Acetone 3 5000 2000
Stage I
2 Acetonitrile Stage II 2 410 410
3 Toluene Stage I 2 890 890
4 Ethyl acetate Stage I & Stage II 3 5000 3000

Di-isopropyl
5 Stage II -- -- 700
ether (DIPE)

OPEN PART

Following table gives the level of residual solvents present in different batches
of Quinapril HCL:
Sr. Tests Results

Specification
No. Validation B. No. QN-17020 QN-17022 QN-17023
Residual Solvents
1 Acetone ND ND ND NMT 2000 ppm
2 Acetonitrile 25 ppm 21 ppm 17 ppm NMT 410 ppm
3 Di-isopropyl ether ND ND ND NMT 700 ppm
4 Ethyl Acetate 32 ppm 68 ppm 1787 ppm NMT 3000 ppm
5 Toluene ND ND ND NMT 890 ppm
ND: Indicates not detected

The results indicate that the residual solvents are well controlled.
After review of the 20 batches data, the specifications for residual solvents would be
tightened.

OPEN PART

Specific discussion on possible genotoxic impurities:
Genotoxicity of Quinapril Hydrochloride & Impurities:

The starting materials used for the manufacture were benzyl 1,2,3,4-
tetrahydroisoquinoline-2-carboxylate p-toluenesulphonate and ECPP alanine. These two
raw materials are condensed with each other in presence of dicyclohexyl carbodiimide
and 1-hydroxybenzotriazole to give an intermediate benzyl quinapril salt with maleic
acid, which on Debenzylation gives Quinapril hydrochloride.
Quinapril hydrochloride is an old established drug patented in US 4,344,949. It is used as

Antihypertensive.
Carcinogenicity
Quinapril hydrochloride was not carcinogenic in mice or rats when given in doses up to
75 or 100 mg/kg/day (50 or 60 times the maximum human daily dose, respectively, on a
mg/kg basis and 3.8 or 10 times the maximum human daily dose on a mg/m2 basis) for
104 weeks.
Mutagenicity
Neither quinapril nor quinapril at were mutagenic in the Ames bacterial assay with or
without metabolic activation. Quinapril was also negative in the following genetic
toxicology studies: in vitro mammalian cell point mutation, sister chromatid exchange in
cultured mammalian cells, micronucleus test with mice, in vitro chromosome aberration
with V79 cultured lung cells, and in an in vivo cytogenetic study with rat bone marrow.
There were no adverse effects on fertility or reproduction in rats at doses up to 100
mg/kg/day (60 and 10 times the maximum daily human dose when based on mg/kg and
mg/m2, respectively).

OPEN PART

Impurities in Quinapril hydrochloride

Following are the starting materials and reagents used in the synthesis of Quinapril
Hydrochloride:
1. Benzyl 1,2,3,4-tetrahydroisoquinoline-2-carboxylate p-toluenesulphonate and

2. ECPP alanine (2-Ethoxycarbonyl-3-phenyl propyl alanine)
The above starting materials do not have any structurally alerting functional groups and
hence are not known to have any genotoxic potential. The formation of any p-
toluenesulphonate esters (genotoxic) is not possible as there are no alcohols being used
in the synthesis in presence of the p-toluene sulphonic acids.
Also used in the synthesis are the compounds maleic acid, di-cyclohexyl carbodiimide
and 1-hydroxybenzotriazole.
Maleic acid is not known to be genotoxic as per the reference:

http://www.epa.gov/opprd001/inerts/maleic.pdf
In the reaction the di-cyclohexyl carbodiimide (DCC) is used as a condensing agent

along with 1-hydroxy benzotriazole as an active ester generating agent. After reaction,
these two reagents along with the byproduct di-cyclohexyl urea are filtered off, the
filtrate then washed consecutively with sodium bicarbonate solution and water, to
remove these impurities. Though these are not known to be genotoxic they are
particularly removed at this stage. The subsequent steps of hydrogenation and salt
formation do not involve any other reagents known to be toxic, or the reactions known to
generate any impurities.
Maximum daily dose: 40 mg per day.

OPEN PART

The EP 49,605 equivalent to the US 4,344,949 [both 1982 to Warner-Lambert] had been
adopted for the synthesis of Quinapril Hydrochloride, the impurities listed in US
Pharmacopoeia are the impurities expected in Quinapril Hydrochloride. The process
being the same as the innovator’s process all impurities formed are also expected to be
the same as that of the innovator’s product.
Hence the impurities of have no genotoxic potential.
There is no evidence that Quinapril Hydrochloride with current permitted levels of

impurities exhibits genotoxicity.
Hence it fulfills all 3 criteria as specified in POTENTIALLY GENOTOXIC

IMPURITIES AND EUROPEAN PHARMACOPOEIA MONOGRAPHS ON
SUBSTANCES FOR HUMAN USE, published in Pharmaeuropa Vol. 20, No. 3, July
2008:
Substance included in a medicinal product authorized before the issuance of CHMP

guidelines - EMEA/CHMP/QWP/251344/2006 dated 28 June 2006:
- PGI expected from synthetic route of first authorized product
- Subsequently authorized products (if any) have no expected PGI or same
- PGI as the first authorized product at same or lower level and
- No data showing genotoxicity.
Therefore Quinapril Hydrochloride with the currently permitted levels of impurities as

specified in Ph. Eur., does not exhibit genotoxic potential.
References:
1. CHMP guidelines - EMEA/CHMP/QWP/251344/2006 dated 28 June 2006.
2. POTENTIALLY GENOTOXIC IMPURITIES AND EUROPEAN
PHARMACOPOEIA MONOGRAPHS ON SUBSTANCES FOR HUMAN USE,
published in Pharmaeuropa Vol. 20, No. 3, July 2008.

OPEN PART

3.2.S.4
CONTROL OF DRUG
SUBSTANCE
January, 2020 3.2.S.4 CONTROL OF DRUG SUBSTACNE Page 1

OPEN PART

3.2.S.4.1 SPECIFICATION
Specification of Quinapril Hydrochloride as per USP is attached on following

pages.
Specification Number: AQC/SP/FP/001
Version Number: Rev-09
January, 2020 3.2.S.4.1 SPECIFICATION Page 1

[ UNCONTRO~L~__fil
@ Aarti Indu stries Limi ted
Unit-I V, E- 50, MIDC , Tarap ur. Taluka & Di st: Palghar, Pin:
401 506, INDIA.
"I. .I A ~
' • r,,..n ,r
Quali ty Contr ol J.l" LJLIJ J. L l\. \.., V 1 1
ll.<>rli lnrl1 ,~trigc I +,-1
Finished Product Specification
Unit - IV
Finished Produ ct Name : Quinapril Hydrochloride
Page No.: 1/3
Specification No. : Effective Date: Supersedes : Revision No.:
AQC/SP/FP/001 08/03/19 12/03/ 18
Material Code: 09
QN STP No.: AQC/ST/FP/001
Reason for chang e: CC No.: QC/1 9-025
Review Date 08/03/24
Prepared By Checked By Authorized By
Trupti Patil Mahendra Girase Shamsundar Desai
07/03/20 19 07/03/2019
Officer / Executive - Quality Control Dept. Head - Quality Contr 07/03/2019
ol QA Head
Reference: USP and In-hou se
Molecular W~ight: 474.98

I.U.P.A.C. Name: (S)-2-[(S)-N -[(S)- 1-Carboxy-3-phenylprop
yl]alanyl)-1,2,3,4-tetrahydro-3-
isoqui nolinecarboxylic acid, I -ethyl ester, monohydrochloride
Structural Formula:
__::c::::: x: ~ ,N
0
.
c:r - . 0::iOH HCI
Category: Antihypertensive
Packing: Quinapril hydrochloride is packed in double polyth

ehe bags i.e outer black antistatic
polyethylene bag and inner natural antistatic polyethylene bag
under nitrogen, these both bags are
separately twist tried and fasten using a nylon fastener. These
bags are placed in triple laminated
sun barrier bags/pouches. They are placed in HOPE container
is closed with lid to simulate market
condition.
Sampling procedure: The material should be drawn from each

drum with proper labeling. The
sampling should be done as per SOP: Q.CS/010
Sample quantity: For analysis : 1 x 50 g.

For micro analysis : 2 x 10 g.
For control samp~e : 2 x 50 g.
Safety pr~cautions: Use nose mask and hand gloves, safety goggl
e during handling.
Storage condition: Preserve in well closed containers and store
at tempe rature between 2-8°C.
Samp le destruction procedure: The sampl e should be destro
yed as per SOP: QCS/01 7.
::lectronically generated document. Signa ture is not requir

ed. Printed on:08/03/2019 09:49

IUNCONTROLLED I
Unit-IV, E - 50, MIDC, Tarapur, Taluka & Dist:
Palghar, Pin: 401 506, IND IA.
.... • ,....,.,...,-r, r,.n .n,r
Quality Control 1VU- \.u l Ll'\ v V ! !
/\ ~rt; l ~ A ,,..t,jo r I trl
Fini shed Prod uct Specification
Finished Product Name: Quinapril Hydroch lorid Unit - IV
e Page No.: 2/3
Specification No.: I Effective Date: Supersedes: Revi sion No.:
AQC/SP/FP/001 I 08/03/19 12/03 /1 8 09
Mat erial Code: I QN STP No.: AQC/ST/FP/001
Reas on for change: CC No.: QC/ 19-025
Review Date 08/03/24
Prepared By Checked By
Trupti Patil Auth orized By
Mahendra Gira se Sham sund ar Desai
07/03/2019 07/03/20 19
Officer / Executive - Quality Contro Dept. 07/0 3/20 19
Head - Quality Control QA Head
Reference: USP and In-house
Sr. Tests Spec.ifka tion

No.
1 *#$ Description A white to off-white powder, with pink cast at time
s.
2 Solubility Freely soluble in water .
1 Identification Tht! Infra red spectrum of lt!sl sample should -
ft A) Ily IR Spectrum be concorciant with
similar preparation of that of Quinapril hydrochl
*#B) By HPLC oride WS/RS.
The retention time of the major peak in the chro
matogram of assay
preparation should l:)e correspond to the chro
matogram of the
4 *Specific optical rotation Between +14.4° and
+15.4° at 25°C on anhydrous basis .
5 *#$ Wate r Content Not more than 1.0 % w/w
(By KF)
6 Residue on Ignition Not more than 0.1 % w/w
7 Content of Chloride Not less than 7.2 % and Not more than 7.6 %
(By pote ntiom etry)
8 *#$ Related Compound Related compound A (RCA) : Not more than 0.5 %
(By HPL C)
Re~ated compound B (RCB) : Not more than 0.5 %
Any unknown impurity (AUI) : Not more than 0.10 %
Total impurities : Not more than 2.0 %
9 *#$ Assay Not less than 98.5 % and Not more than 101.5 %
on anhydrous basis.
(By HPLC)
10 Residual solvent Acetone : Not more than 2000 ppm.
(By HSG C)
Acft onitr ile : Not more than 410 ppm.
Di-isopropyl ether : Not more than 700 ppm.
Ethyl Acet ate : Not more than 3000 ppm.
Toluene : Not more than 890 ppm .
:lectronically gen erat ed document. Signatur

e is not required. Printed on:08/03/2019 09 :49

LUNC<i,NTRO~@
Unit-IV, E- 50, MIDC, Tarapur, Taluka & Dist: Palghar, Pin: 401 506, INDIA.
Quality Control
... "
lVlt\u l
. ·-
C,1'.
r,r,.n,r
\...,Vr l
I
r,. -, ri · 1-_., ,,-+,:~- I +A
Finished Product Specific ation
Unit - IV
Finished Product Name: Quinapr il Hydroch loride Page No.: 3/3
Specification No.: EffectiYe Date: Supersedes: Revision No.:
AQC/SP /FP/001 08/03/19 12/03/18 09
Material Code: QN STP No.: AQC/ST /FP/001
Reason for change: CC No.: QC/19-025 Review Date 08/03/24
Prepare d By Checked By Authorized By
Trupti Patil Mahend ra Girase Shamsundar Desai
07/03/20 19 07/03/20 19 07/03/20 19
Officer I Executiv e - Quality Control Dept. Head - Quality Control QA Head
Referen ce : USP and In-house
Additional Test
Sr. Tests Specific ation

No.
1. Palladiu m content Not more than 0.001 % [10 ppm)
* This test applicable for stability specification,
# This test applicable for working standard,
$ This test applicable for Re-testing.
:lectron ically generated document. Signature is not required . Printed on :08/03/2019 09:49

OPEN PART

3.2.S.4.2 ANALYTICAL PROCEDURE
Analytical procedure for analysis for Quinapril hydrochloride as per USP

attached on following pages.
Test procedure number: AQC/ST/FP/001
Version Number: Rev-09
January, 2020 3.2.S.4.2 ANALYTICAL PROCEDURES Page 1

OPEN PART

3.2.S.4.3 VALIDATION OF ANALYTICAL PROCEDURES
The analytical procedures as described in USP have been adopted for the testing of
Quinapril Hydrochloride and compliance to the specifications as per USP.
The suitability of these methods under actual conditions of use was verified
{1225}.
The residual solvents used in the manufacturing and purification of Quinapril

Hydrochloride are – acetone, acetonitrile, toluene, ethyl acetate and di-isopropyl
ether. Hence in the Residual Solvents Method validation all these solvents were
included. In addition IPA that could be present in QN – II was also included for the
purpose of method validation.
No class 1 solvent is used in the manufacturing process.
Analytical Method validation was carried out as per ICH Guide lines Q-3C dated
25th November 2005, the validation report of residual solvent validation is provided
The complete validation report of related substance method validation by HPLC as

per USP along with chromatograms is provided.
Assay method validation by HPLC as per USP along with chromatograms is is

provided.
The method verification report for the content of S,R-isomer in starting material S1-
compound (ECPPA) is provided.
Validation report details:

Sr.No. Method Validation No. Page No.
1 Related substances by HPLC AH/ADL/VAL/10/36 2- 140
2 Assay by HPLC USP 32 method 141- 166
3 Residual Solvents by GC AH/ADL/VAL/05/09 167- 395
Chiral Purity of S-1 AH/ADL/VAL/18/21
4 compound (ECPPA) by 396- 422
HPLC (R-Isomer)
5 Elemental Impurity QC/MV/RP/19/10 423-617
Validation
January, 2020 3.2.S.4.3 VALIDATION OF ANALYTICAL PROCEDURES Page 1

PROTOCOL NO. : AWADLNALiO5109
Report on
ANALYTICAL METHOD
VALIDATION OF
RESIDUAL SOLVENTS
QUINAPRIL HCl
REPORT NUMBER: AWADLNALIO5109

RESIDUAL SOLVENTS - ANALYTICAL METHOD VALIDATION
To validate the analytical method for the detection & quantification of the residual
solvents in Quinapril Hydrochloride.
2.0 SCOPE:
The scope of the report is limited to the quantification of residual solvents in

Quinapril Hydrochloride.
3.0 RESPONSIBILITY:
Method validation of residual solvents in Quinapril Hydrochloride was carried out

by Analytical Development Laboratory of Aarti Industries Limited, Dombivli,
Thane - a division of Aarti Industries Limited.
The validation team:
Name Designation
Mr. Madhav Rane Executive
Mr. Mahendra Girase Executive
Mr. Jayantb Mhetar Sr. Executive
PREAMBLE:
Quinapril Hydrochloride is being manufactured since September 2005.
The manufacturing of Quinapril Hydrochloride involves 2 stages viz.:
1. (S) 1,2,3,4-Tetrahydroiso quinokine-3- carboxylic acid and the preparation

of maleic acid salt of benzyl quinapril..
2. De-benzylation of benzyl quinapril and hydrochloride salt isolation.
n- Pentane, acetone, isopropyl alcohol (IPA), acetonitrile (ACN), di isopropyl ether

(DIPE), ethyl acetate and toluene are used in the manufacturing process of
Quinapril Hydrochloride.
Acetone and isopropyl alcohol (IPA) are used in the manufacture of (S) 1,2,3,4-
Tetrahydroiso quinoline-3- carboxylic acid and the preparation of rnaleic acid salt
of benzyl quinapril.
Page 1 of 82

QUINAPlUL HYDROCHLORIDE USP
-
Hence for the Analytical Method validation the solvents i.e n- Pentane, acetone,
isopropyl alcohol (IPA), acetonitrile (ACN), di isopropyl ether (DIPE), ethyl
acetate and toluene were included in the Analytical Method validation carried out
in August 2005.
Analytical Method validation was carried out as per ICH Guide lines Q-3C dated
1 7 July,
~ ~ 1997.
For Class 2 solvents - Acetonitrile (ACN) and Toluene;
For Class 3 solvents - n-Pentane, acetone, ethyl acetate and isopropyl alcohol
(FA)
Di-isopropylether (DIPE) (not included in class 2 & class 3) using in-house
method.
No Class 1 solvent used in the manufacturing process.
Page 2 of 82

4.0 LIST OF SOLVENTS USED IN THE MANUFACTURING OF QUINAPRlL

ALONG WITH ICH & INTERNAL LIMITS
I I, n-Pentane Stage I1 3 5000 5000

2. Acetone Stage I 3 5000 5000
3. lsopropyl Alcohol (IPA) Starting Material 3 5000 1000
4. Acetonitrile (ACN) Stage II 2 410 410
5. Di-isopropyl ether (DIPE) Stage I1 -- -- 750
6. Ethyl acetate Stage I and I1 3 5000 5000
-
7. Toluene Stage I 2 890 890
5.0 PARAMETERS SELECTED FOR VALIDATION:
9 Specificity and selectivity

> Precision
> System precision
9 Method precision
> Linearity and Range
> Limit of Detection (LOD) and Limit of Quantitation (LOQ)
P Accuracy / Recovery
P Ruggedness (Intermediate Precision)
9 Robustness
P Flow rate _+ 10%
-
> Flow rate 10% i.e. 1.53ml/min
> Flow rate +lo% i.e. 1.87mVmin
P Incubation time 20%+
> Incubation time -20% i.e. 16 min
k Incubation time +20% i.e. 24 min
-- - -. - - - --
Page 3 of 82

7

6.0 METHODOLOGY:
6.1 Instrument:
Gas Chromatograph with Head Space Shimadzu AOC-5000 auto injector

Data acquisition GC solution.
6.2 Reagents:
2 Acetone S 15FS50622 HPLC Merck

3 lsopropyl Alcohol (IPA) 7203 6504-3 HPLC Qualigens
4 Acetonitrile (ACN) 0244 GR Qualigens
5 Di-isopropyl ether (DIPE) L03A-0303-09 12-13 LR S.D. Fiqe
6 Ethyl acetate SJSSF5569 GR Merck
7 Toluene SBSSF55093 HPLC Merck
8 N, N dimethyl formamide (DMF) 74 106510-3 HPLC Qualigens
6.3 Glassware: A class certified. Make - BOROSIL
Page 4 of 82

6.4 GC AND HEAD SPACE CONDITIONS:
Column DB624, Bonded phase, L - 30 meters; ID - 0.53 mm; Film

thickness - 3p.
GC Shimadzu make - model GC-17A
Software GC Solution.
GC Conditions Head space Conditions

40°C for 5 min; then (38°C Oven Temp 110°C
lmin to 150°C, @40°C lmin to
Oven Temp. Syringe 12O0C
240°C Final Temperature - r
1 1 240°C Hold for Y ~ i n u t e s . I ~ttention 10 I
Detector Temp. 250°C Injection Volume 1 ml
Injector Temp. 250°C Incubation Time 20 minutes
- Flow rate 1.70 ml 1 Min. Cycle Time 40 Minutes
Carrier Gas Nitrogen
Operation mode Spkit ratio 5
Run Time 25 minutes
i
Standard Preparation: Prepare standard solutions as per the procedure given below.
Transfer 5.0 ml of blank, standard solutions into each 20.0 ml vials.
Table 6.4.1
2 ml Solution (A)
Page 5 of 82

Test Preparation: Transfer 0.2g of the sample into the vials and add 5.0 ml of N, N
dimethyl formamide (DMF).
Close the vials with septum, place cap and crimp to seal. Place the vials in a
predetermined sequence in the incubator where in the vials would be heated to approx
110°C for 20 minutes to facilitate the transformation of solvents in to vapours phase.
Calculations:
Test area X wt of std (gm) X dilution of sample

Residual Solvent (ppm) = ............................................................... x lo6
Standard area X std dilution X wt of sample (grn)
7.0 EXPERIMENTAL DATA & RESULTS:
The solution preparation, results are given under each analytical method validation
parameter:
Page 6 of 82

RESIDUAL SOLVENTS- ANALYTICAL METHOD VALIDATION
QUnVAPRIL HYDROCHLORIDE USP
The analytical method validation of

n- Pentane, acetone, isopropyl alcohol (IPA),
acetonitrile (ACN), di isopropyl ether
(DIPE), ethyl acetate and toluene
Page 7 of 82

SPECIFICITY
AND
SELECTIVITY
Back to top
Page 8 of 82

7.1 SPECIFICITY:
Specificity was determined by injecting individual solvents i.e. n- Pentane, acetone,

isopropyl alcohol (IPA), acetonitrile (ACN), di isopropyl ether (DIPE), ethyl acetate
and toluene. The resolution of each solvent fiom other was demonstrated by
comparing the Retention time of the solvents.
Acceptance criteria:
All the peaks should be well resolved from each other
7.1.1 SPECIFICITY SOLUTIONS PREPARATION:
7.1.1.1 Blank: N,N dimethyl formamide was used as blank:

7.1.1.2 Diluent : N,N dimethyl formamide
7.1.1.3 Specificity solutions:
Specificity solutions - individual solvents were prepared in the following manner:
TABLE - 7.1.1.3 - 1
1. n-Pentane 1.OO 1.160 a lOOml(A) 2 ml (A) 2 100ml 232

2. Acetone 1 .OO 1.131 * 100ml(B)..
2 ml (B)a 100mi 226
- --
3. IPA 0.20 0.265 = 100 ml (C) 2 ml (C) = 1OOml 53

4. ACN 0.08 0.091 ~100ml(D) 2 ml (D) 3 lOOml 18.2
5. DIPE 0.15 0.190 s100ml(E) 2 ml (E) 3 lOOml 38
6. Ethyl acetate 1 .OO 1.250 s 100 ml (F) 2 ml (F) a lOOml 250
7. Toluene 0.18 0.229 3 100 ml (G) 2 rnl (G) 3 100mI 45.8
Page 9 of 82

- - - -

L
Selectivity - mixture of solvents were prepared in the following manner:
TABLE - 7.1.1.3 -2
n-Pentane
Acetone 1.131
0.20 0.265
4.
I
ACN
I
0.08 !
I
O.O9'
1 a 100 ml
(Solution A) ,
2 ml Solution (A)
lOOml
5. DIPE 0.15 0.190
6. Ethyl acetate 1.00 1.250
1 7. 1 Toluene I 0.18 1 0.229 I
7.1.2 RESULTS:
Blank Chromatogram No.: 1 & 2
TABLE - 7.1.2 -1
Page 10 of 82

7.1.3 INFERENCE:
The results indicate that:
1. All the solvent peaks were well resolved.
2. They were well separated from each other.
3. The retention time obtained in the individual injections was concordant

with those obtained in the solvent mixture.
7.1,4 CONCLUSION: Meets the acceptance criteria for specificity
7.1.5 CHROMATOGRAMS: Chromatograms are given on the following pages.
1. 1&2 Blank
2. 3 n-Pentane
3. 4 Acetone
-
4. 5 IPA
5. 6 ACN
6. 7 DlPE .
7. 8 Ethyl acetate
8. 9 Toluene
9. 10 Mix Std (Selectivity solution)
Back to top
Page 1 1 of 82

Sample Information
Analysis Date & Time : 8/16/20051 l:37:17 AM
User Name : Admin
S a m ~ l Name
e :QUINAPRIL
sample ID : BLANK
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATIOMQNNVfiID\I
60805\QN_Ol.gcd
Method Name : E:\GC-I 7 A\GC-METHODS\QUINAPRIL.gcm
Instrument no :M A D W 0 5
Intensity ~ - - -~ ....
I
I
-
Peak Table Channel 1
PRODUCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATlON

PARAMETER :SPECIFICITY
BIN NUMBER : .& INST.NO, :AH/ADWDS
DONE BY:
DATE: as\slo<

Sample Information
Analysis Date & Time : 8/16/2005 12:18:03 PM
User Name :Admin
Sample Name : QUINAPRIL
Sample ID : BLANK
Data Name : E:\GC-I 7 A\GC-Data\QN-VALIDATION\QNNVALID\l
60805iQN-02.gcd
Method Name : E:\GC-17 A\GC-METHODS\QUh'APRIL.gcm
Instrument no : AWADLIOS
Intensity _ _ - - _ - _ - - _ - . - - 7
- - - - I -
,------7-----
7 ----- 4
0 10 20
min
-
PRODUCT NAME : QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER : SPECIFICITY
BIN NUMBER : 2 1NST.NO. :AH/ADWOS
CHROMATOGRAM N A M E '
DATE : .2~\2117< DATE :

AARTl HEALWARE LTD.
AQI Ow$Sra_nllW Bnll'tl IhaWSMUES L4n;rrh;D
Sample Information
User Name : Admin
Sample Name : QUmAPRIL
Sample ID : N-PENTANE
Data Name : E:\GC- I7 A\GC-Data\QN-VALIDATION\QN-VALID\
160805\QN-03.gcd
Method Name : E:\GC- 17 A\GC-METHODS\QUlNAPRIL.gcm
Instrument no :AHIADWOS
Intensity --
-
Peak Table Channel 1 ,
---
--
.- -
-- R e t . T i e N a m e . - A r e a -
Peak# - - Areayo
- ,
i
1 9.023 Z P E N T A N E . 2. 1 6 9 9 0 6 0 . 100-0000 --
TotalpJ - - 2 1 6 9 9 0 6 0 . _lO_o.O! --
PRODUCT NAME :QUINAPRiL HCL RESIDUAL SOLVENTS VALIDATION

BIN NUMBER: 3 1NST.NO. : AWADM5
CHROMATOGRAM NAME.
DATE : 24\9\0< DATE :

AARTl H E A l M A R E LTD.
Apt WVttilBN W XARYI 89IWSTWIEB LMI'nB
Sample information
Analysis Date & Time : 8/16/2005 1 :39:21 PM
User Name : Admin
Sample ID :ACETONE
Data Name : E:\GC-17 A\GC-Data\QN V A L I D A T I O N \ Q N ~ V A L I D \ ~ ~ ~ ~ ~ ~ \ Q N ~ O ~ . ~ ~ ~
Method Name : E:\GC- 17 A\Gc-METHODS\QUINAPR~L.~C~
Instrument no : AHIADLIOS
Intensity - . - - _ . - . p - - - p - pI -
750000
i:
250000-- I\ I :
I
ii '
.
~i I
.:
'y,
.$.L,'
'
ii
'" = ,,
. . \__
---- --
. -- -~.-
0 - -. - -A -
_ __
-- --
-,-. -.
~p
.-
., - r-_..___~ -
0 10 20
min
-- - - --
Peak Table - Channel 1 - .- -
Peak#
- ' Ret.Tirne Name - 4.- &!L - ,
- -~rd-- -
-1 .- -
10.152 ACETONE 2355531 A 1@.0=op- 1
Total _ . - --- - --
2355137 - - lOo,o_OW
PRODUCT N A M E :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

BINNUMBER: 4 INST.NO. : AWADWOS
DATE :

Sample Information
User Name : Admin
Sample ID : IPA
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATION\QN-VALID\!
60805\QN-05.gcd
Method Name : E:\GC-17 A\GC-METHODS\QUINAPRIL.gcm
Instrument no : AHIADW05
Intensity ~ - - .... -~ -- -. - --
-. .- . - -. - - --
-.
250000-- s.
w
N
,
,
8
,
I
; ! :
4
! -.\;,
'
8
8',
'.
'<.
.
I -.%-,.\.-
,'
*".<
/:
0
~ -
..
. _
-.-.--I
_.-
- --
-
-7 --
_
. - -- .. --.
_-
- - -. -- .- .- _._
- ...
----
--- ,
20
._ -- .-
.. . - .
0 10
min
, Peak Table - Channel 1- - - A - --

Area I b a s I
- - l o ~ O-
Peak# _.Time 1 N-me- --- -
-
I -
_324 1pA A 6 - 3 8 ~
-Total , .-- -. - -- --660538-
~ 0 ~ 0 0 - -
PRODUCT NAME : QUlNAPRlL HCL RESlDUAL SOLVENTS VALIDATION

PARAMETER : SPECIFICITY
BIN NUMBER: 5 1NST.NO. : AH/ADL/OS
CHROMATOGRAM NAME
DONE BY:
DATE : DATE :

Sample Information
User Name : Adrnin
Sample Name :QUINAPRIL
Sample ID : ACN
Data Name : E:\GC-17 A\GC-DatdQN-VALIDATION\QN~VALID\160805\QN-06.gcd
Method Name :E:\GC-17 A\GC-METHODS\QUINAPRIL.gcm
Instrument no :AH/ADL/OS
Intensity -- . -- ,
-- p- - - -- .
- - - -
6
250000 -
5
01
00 ' 1.2
1
0
I
ii
"i
'--
,x .
--..
0
-
-
.
- .
-~
,.-.---.--
-
11
L ------.---
.-..,
- ---
~
\.\-A-
J:
..I
0 10 20
min
-
Peak# -Ret.Time _ Name.
.- -
-
Peak Table
-
;+_ -
- C--h a n n e l I
A r e ~ - -- ~reaO/o =,
L . 10.891 + A m- -- -- -
776417- ,-
100.0000 -- --
Total -- - 1 7764 17-_ L~OOQo- --
PRODUCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

1 PARAMETER :SPECIFICITY
BINNUMBER: 6 INST.NO. : MADLIOS
DATE : DATE :

Sample Information
Analysis Date & Time : 811612005 3:41:16 PM
User Name :Admin
Sample ID : DIPE
Data Name : E:\GC- 17 A\GC-D~~~\QN-VALIDATION\QN-V~ID\I
60805\QN-07.gcd
Instrument no : AWADLIO5
Intensity -
. --- --- - - - -
--- 7----
- -
-7 - I
1 E
I
750000-- :I 2i 8 I
11 5 ' I
I
500000-
~l I
I I
I I
1;
11 ~;
250000
iI :J,2
I I .
!
, - - \
-'1 ',. ..\
" .- .-. _
o,.. -- .... ~
1 ~ -
---, -~ ~- - 7--.-
- . ---.
. .. . - - -. - , - -.-..- - ---
0 10 20 min
. - - --
-
Peak Table Channel 1 _ -- -- 7
Pe&#
- _Ret.Tirne! N a m e -4 - -Area-- -L-A--- - 7
-1 - -12.9644 DIPE -- - - 6018914 _!oo&o~ --
T o t a l 1 -
6018914 - - 10!.!~0- -

PARAMETER : SPEClFIClTY
BIN NUMBER: ? 1NST.NO. :A W A D W
CHROMATOGRAM NAME
DATE : -L
,a \$\d

AARTl HEALTHCARE LTD.
AP1 OWISION OF A M 7 7 IMWSTRIES L W E D
Sample Information
Analysis Date & Time : 8/16/2005 4:22:03PM
usedame :Admin
Sample ID :ETHYL ACETATE
Data Name : E:\GC-17 A\GC-Data\QN-VALIDATIOMQN-VALID\l
60805\QNd08.gcd
Method Name : E:\GC- 17 A\GC-METHODS\QUINAPRIL.gcm
Instrument no - - '-5
: AHIADWO
20
min
-- - - -- --
Peak Table - Channel 1 , -.
P&# Ret.Time- N =
:- - -
Area , - - A ~ E Z B ~
-4.279 ETHYLACETATE- - 93688 -. -_ m . O O O o l
T_otal-_ -- - -. - -- -93688 100,oom --

BIN NUMBER : 8 1NST.NO. : AWADVOS
I
CHROMATOGRAM NAME
DATE : 24\6 b4 DATE :

AARn HEALTHCARE LTD.
A P WLSW
~ OT ~ Yw wIs n x s ifarmo
Sample Information
Analysis Date & Time :8/16/2005 5:02:52 PM
User Name : Admin
Samole Name :OUTNAPRIL
sample ID
Data Name
Method Name
Instrument no
-
Peak Table Channel L
*--.
I
-
--
Peak# + R e t . T h
Name
, B ~ O _IOLUJE
~ _
--
--._ A r e a - - _Areayo
-
,r 7 7 m -..- m o o o o _ ~
-
- ~~
TOG%-_ - - -- I 1771533 ! ~lOO.OOll&
PRODUCT NAME :QUMAPRIL HCL RESIDUAL SOLVEN'B VALIDATION

I PARAMETER : SPECIFICITY
BIN NUMBER : Q MST.NO. :AHIADWOS
CHROMATOGRAM NAME
DONEBY: :
DATE : DATE :

Sample Information
User Name : Admin
Sample ID : MIX STD
Data Name : E:\GC-I 7 A\GC-Data\QN VALIDATION\QN-VALID\] 60805\QN-10.gcd
Method Name : E:\GC-I 7 A\GC-METHO~S\QUWAPRIL.~C~
Instrument no : AHIADWOS
Intensity
~00000 .-
- ---- - - 7 -
20
-
-- -
min
-
-
Peak Table Channel 1 -
P;&&-R~~.T=
I - --
Name
----- 7 Area
T--
~ r e a %
A
--
-
7
-
r 2 _
-- 8.948
- N-PENTANE
10.269 ACETONE -
.
-
,
17190474- - .
- 1330655 -
83.8425 -1
-
6.4900 --
115070 1 . -0.5612 - ,
3 _ 1 tO559-LPA-
3 9 8 7 5 1 .-_9.1945 -.A
-
4 10.957 S N -! -
- 3,4621 - -
-
3- - - - 12.991 =PEP
-
,. 709963 --
h - 14,261 ' ETHYL ACETLATE 9 2 m 3 - , -- 4.4943- 4

-
. 7 19387 TOLUENE --- 19572 - 0.9545- -

-Total _ - ,- -- - -- 20503292
- l O & L ? ! L--
PRODUCT NAME . QUTNAPRIL HCL RESlDUAL SOLVENTS VALLDATION I
PARAMETER. SPECIFICITY
BIN NUMBER 10 INST.NO AWADUOS I
CHROMATOGRAM NAME
mNEBy & CBECIEDBY
DATE \s$
.W\S:

QUINAPFUL HYDROCHLORIDE USP
PRECISION
SYSTEM PRECISION
Back to top
Page 12 of 82

7.2 SYSTEM PRECISION:
System precision was determined by injecting the mixture of 7 solvents - viz -

n-Pentane, acetone, isopropyl alcohol (IPA), acetonitrile (ACN), di isopropyl ether
(DIPE), ethyl acetate and toluene. The mixture was injected 6 times and the
retention time & Area reproducibility was determined
Retention Time % RSD - NMT 2.0%.

Area % RSD - NMT 15.0%.
7.2.1. STANDARD SOLUTIONS PREPARATION:
7.2.1.1 Blank: N,N dimethyl forrnamide was used as blank

7.2.1.2 Diluent: N, N dimethyl formamide.
7.2.1.3 System Precision
System Precision solutions were prepared by mixing all the solvents in the following
manner:
TABLE
2. Acetone 1.OO 1.070

3. IPA 0.20 0.203
!
1 I
4. ACN 0.08 O'Osl

0.160
I ==? 100 ml
(Solution A)
2 rnl Solution (A)
3 1 OOml
1.050
Toluene 0.18 0.182
Page 13 of 82

QUINAPRIL HYDROCKLORIDE USP
7.2.2 RESULTS:
Blank Chromatogram No.: 11

TABLE - 7.2.2 1 -
SD 0.049 0.054 0.055 0.060 0.059 0.059 0.048

%RSD 0.55 0.52 0.52 0.55 0.46 0.42 0.24
Acceptance
criteria
NMT 2.0%
-
TABLE 7.2.2 2 -
Average 15057007 1063845 92692 34830 620329 793336 161342

SD 1927203.102 124327.747 13058.966 4016.1 18 75303.839 97238.125 19828.665
%RSD 12.80 11.69 14.09 1 1.53 12.14 12.26 12.29
Acceptance
criteria NMT 15.0%
Page 14 of 82

7.2.3 INFERENCE:
1. The O h RSD of retention time was 0.24 to 0.55.
2. The % RSD of area was 11.04 to 12.80.
7.2.4 CONCLUSION: Meets the acceptance criteria for system precision.

7.2.5 CHROMATOGRAMS: Chromatograms are given on the following pages along
with calculation sheet.
TABLE - 7.2.5 - 1
100% STD-4 (System precision)

6 16 100% STD-S (System precision)
7 17 100% STD-6 (System precision)
Back to top
Page 15 of 82

7.3 METHOD PRECISION
Back to top
Page 16 af 82

QvnuAPRu HYDROCHLOrUDE USP
7.3 METHOD PRECISION:
Method precision was determined by injecting six sample preparations from the
same batch - batch number - AH /05@6/108and quantifying the solvents present
in the batch as well determining the % RSD of the retention time, area and
concentration of the solvents.

Content % RSD - NMT 15.0%
7.3.1.1 Blank : N,N dimethyl forrnamide was used as blank:

7.3.1.2 Diluent : N,N dimethyl fomamide
7.3.1.3 Method Precision
Method Precision solutions were prepared by taking six different weight of batch number -
A l l ,0506i108, and estimating the content of residual solvents:
TABLE - 7.3.1.3 I -
Page 17 of 82

QUINAPRn, HYDROCHLORIDE USP
7.3.2 RESULTS:

TABLE - 7.3.2 - 1
Average NA NA NA NA NA NA NA
SD NA NA NA NA NA NA NA
lAccep-e I
criteria -- - -
- - - - - -
NMT 2.0%
TABLE - 7.3.2 - I
Page 18 of 82

RESIDUAL SOLVENTS - ANALYTICAL METHOD VALJDATION
QUINAPRlL HYDROCHLORIDE USP
7.3.3 INFERENCE:
The area for n-Pentane, acetone, isopropyl alcohol (IPA), acetonitrile (ACN),
di isopropyl ether (DIPE), ethyl acetate and toluene was not detected in sample.
The % RSD of content was not applicable.
7.3.4 CONCLUSION: Meets the acceptance criteria for method precision
Back to top
Page 19 of 82

Sample Information
Analysis Date & Time : 8/ 1612005 6:24:33 PM
User Name : Admin
Sample ID :BLANK
Data Name :E:\GC- 17 A\GC-Data\QN-VALIDATION\QN-VALID\I
60805\QN-11.gcd
Instrument no : AHIADLfOS
Intensity
500000
o--
0
.
-
-- . -
-
-- - -.
--
.
.-
.
I
10
- - . --
..- --
2b
_- -
.
-
p
a
min
Peak Table - Channel 1

] PARAMETER :SYSTEM PREClSlON
1
BIN NUMBER: /\ INST.NO. :AH/ADL/OS
CHROMATOCRAM NAME :
DONEBY: CHE
DATE : a4ls\ag

S a m l e Information
Analysis Date & Time : 8/16/2005 7:05:18 PM '
User Name : Admin
Sample ID : 100% STD 1
Data Name : E:\GC-17 A\GC-Data\QN VALIDATIOMQN VALID\i 60805\QN-12.gcd
Method Name : E:\GC- 17 A\GC-METHO~S\QUINAPRIL~S~gcm
Instrument no : AWADLI05
20
min

PARAMETER :SYSTEM PRECISION
BIN NUMBER : !2 INST-NO. : AWADMS
DATE :

Sample Information
User Name : Admin
Data Name 3.gcd
:E:\GC-17 A\GC-Data\QN-VAL1DATIOMQNNVALID\160805\QN-1
Method Name : E:\GC-17 A\GC-METHODS\QUINAPRn.gcm
Instrument no : AH/ADLJOS
Intensity
20000001 - - -- - -
P R O D U n NAME :QUMAPRIL HCL RESIDUAL SOLVENTS VALIDATION

1 CHROMATOGRAY NAME :
DONEBY:
DATE : ~Y\~\:\os
+ IOQ'/-
DATE :
S7-m 7- 4

Sample Information
Analysis Date & Time : 8/16/20058:26:54PM
User Name : Admin
Sample ID : 1 000h STD 3
Data Name : E:\GC-I7 A\GC-Data\QNVALIDATIOMQN-VALID\160805\QN-14.gcd
Method Name :E:\GC-17 A\GC-METHO~~S\QUMAPRIL I SK.gcm
Instrument no : AWADWOS
I --- - - -
p7
-
""~irn~l
8.894
. ---- -
Name
N-PENTANE
Peak- Table - Chqnel I
--
13604011
Area Area%
5.9273
10.221 ACETONE 948732
10.525 , IPA .- - 72959 0.4558
4 10.919 ACN 32197 0.2012
5 . 12.961 DIPE 54913 1
- 6 14.225 ETHYL ACETATE 666898
7 19.755 TOLUENE 132272 0.8264
Total 16006200 1 100.0000
PRODUCT NAME : QUINAPRIL HCL RESlDUAL SOLVENTS VALIDATION

BIN NUMBER : 14 INST.NO. :AWADWOS
DONE BY:
DATE: 24\9\0~ DATE :

Sample Information
User Name : Adrnin
Samnle
r
Name
-- - - ~ - -
: OUINAPRIL
: 1 ' i / o STD 4
~
S G p l e ID
Data Name : E:\GC- I7 A\GC-Data\QN-VALIDATION\QN_VALID\I 60805\QN-15.gcd
Method Name : E:\GC-17 A\GC-METHODS\QUINAPRILlSK.gcm
-
AreaYo
16092962 84.8948
5.8305 -.
I
3.4967 --
4,2358
Total -_ 1 - - -111956358.--- 1_@,0000 J
PRODUCr NAME :QUlNAPRlL HCL RESIDUAL SOLVENTS VALIDATION

BIN NUMBER : MST.NO. :AWADL/OS
C H R O M A T X
DONE BY:
DATE : W\S\QS DATE: Z-G~~'

Sample Information
User Name : Admin
Data Name :E:\GC-17 A\GC-Data\QN-VALIDATION\QNNVALID\1608O5\QN-l6.gcd
Method Name :E:\GC-17 A\GC-METNODS\QUMAPRIL 1SK.gcm
Instrument no :AWADWOS
20
min
- -
Peak Table - ChameJ 1 A
,-Peakff , Ret.Time _ - N N .... Area

1 1 8.954 N-PENTANE
2 10.276 ACETONE -
3 10.575 IPA 0.5039

LA---
5
10.972 ACN
12.983 DIPE
38600
705314
0.1902
3.4748
I
6 14.249 ETHYL ACETATE 866705 4.2700
7 19.770 TOLUENE 166880 0A222
Total 20297720 100.0000
PRODUCT NAME :QUMAPRlL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER : SYSTEM PRECISlON
BM NUMBER : 16 INST.NO. :AWADWOS
DONE BY:
DATE: 24\%\0<

Sample Information
User Name : Admin
S a m ~ l eName :QUINAF'RIL
sample ID : Ibo%S T D 6
Data Name : E:\GC-17 A\GC-Data\QN-VALIDATION\QN-VALID\160805\QN-l7.gd
Method Name : E:\GC- 17 A\GC-METWODS\QUlNAPRIL.gcrn
Instrument no : AWADW05
Intensity
2000000,
1500000
1000000 1
1
0
m
00 1~
7- ;
'~
I
I1 E
i
500000
1 -I
1
I
p i i; -
i0
Eu
6<$
~ $ 4
g
g
u
E
*
2!
9 1 '
~
0 j --
I ~ ' " ~ ' ' ~ ' I " ' r ~ " "
20
min
--
-
Peak Table Channej 1
AT:%:
Area Area%
10.620 PA --
t T:bl 1.-
11.026
13.054 DIPE
I
19.849 TOLUENE -
14.32-4 ETHYL ACETATE
+
,
757474
M L l l
15608677
-
1
-
-
0.2227 --
-- - - _
3.5331
-
4.8529
0,9297
. 100.0000
.
,

BIN NUMBER : INSTJO. : AIUADLlOS
DONE BY:
DATE : U\B\OC

RELATlYE STANDARD DEVIATION
PRODUCI'NAME : RESIDUAL SOLVENT VAWDATlON FOR QUIIYAPRIL BCI
EXPERIMENT : PRECISION
SYSTEM PRECISION FOR RETENTION W E
Sr. No n-ptane Acetone IPA ACN DIPE E Acetate Toluene
Avcrage 8.924 10 248 10.546 10943 12.971 14.238 19.770

sa o 049 o 054 o 055 0060 0.059 0.059 0.048
YsRSD 0 55 0 52 0 52 0 55 0.46 0.42 0 24
D O N E BY:
DATE:

REUTWE STANDARD DEVfATlON
PRODUff NAME : RESIDUAL SOLVENT VAWDATION FORQUINAPR& ECl
EXPERIrn : PBeClSION
SYSfEM PRECISION FOR AREA
Sr No kpcntane Acetone PA ACN DPE E Acetalc Toluene

-
Average 15057619 1 1 70601 93718 1 35060 620943 793610 161993

SD 1926649761 116445 819 11325 065 [ 3872080 74619298 %811972 18716029
%RSD I 2 80 1 1 66 I208 1 1 1 04 I202 1220 1155
-.
DONE BY CHECKED BY'
DATE:

API DNIBKIN OF a n ~~ousnws
mtrqo
Sample Information
User Name : Adrnin
Sample ID : BLANK
Data Name 17 A\GC-Data\QN-VALIDATION\QNNVALID\l
: E:\GC- 60805\QN-1X.gcd
Method Name 17 A\GC-METHODS\QUINAPRIL.gcm
: E:\GC-
Instrument no : AWADL/OS
Intensity
--
500000--- -~ - ~ . -- . .. ~~ -~ .
-r- -
.,
0 - - - - - - --.
. - -
_- . - . I __ - -- - ..-y
--.-
. , - --,-, 7
I -. - -. -- --
0 10 20
min
PRODUCT NAME :QUiNAPRIL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :METHOD PRECISION
BIN NUMBER : 1g 1NST.NO. :AWADLmS
CHROMATOGRAM NAME
DATE: ~ \ $ \ 6
DATE :

Sample information
Analysis Date & Time : 811712005 12:44:08 AM
User Name : Admin
Sample ID : SAMPLE 1
Data Name
Method Name
Instrument no
Intensity
500000- -- -
I,
0 - - - ' L -
- - . . -.-.
I
~ _ _ ...-
0 10 20
min

PARAMETER : METHOD PRECISION
BIN NUMBER : Iq 1NST.NO. :AHIADLmS
DATE : DATE :

Sample Information
Analysis Date & Time : 8/17/2005 1 :20:07 AM
User Name :Admin
Data Name :E:\GC- 17 A\GC-Data\QN-VALIDATION\QNNVALID\
t60805\QN-20.gcd
Intensity
500000 - - -- -- -- - - - - - -- -
I
I
I
400000- I1
I
-- - -- --7 . - - - - - I T -- T - - r---
0 10 20
min
Peak Table - Channel I

I PARAMETER :METHOD PRECISION 1
BIN NUMBER : 0 1NST.NO. :AWADWOS
DATE : DATE :

Sample Information
Analysis Date & Time : 8/17/2005 1:57:01 AM
User Name : Admin
Sample Name : QUNAPRIL
Data Name :E:\GC- 17 A\GC-DatalQN-VALIDATION\QN-VALID\f
60805\QN2I .gcd
Method Name : E:\GC-17 A\GC-METHODS\QUMAPRIL.gcm
Instrument no : AH/ADL/O5
Intensity
~00000. - -- -- --- -- -
pp - - -
17 --- I
I I
I
400000 ~ 1 I
,
I I
300000 - I
j I
i I
I
200000 :I I I
I
I
-

BIN NUMBER : as 1NST.NO. : AHIADWOS
CHROMATOGRAM NAME :
DONEBY: &
-
DATE: 14\8\& DATE :

AARTI HEALTHCARE LIP.
~A
A P ~D ~ ~ ~ BOF Nfln sNDusratcs L#wtr%a
On
Sample information
Analysis Date & Time : 8/17/2005 2:34:00AM
User Name : Admin
Data Name : E:\GC-17A\GC-Data\QN-VALIDATION\QN-VALID\160805\QN-22.gcd
Instrument no : AWADUO5
Intensity
~00000 -- - - --- --- .
- - - - - -. -- -
7
min
PRODUCf' NAME :QUINAPRlL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :METHOD PREClSlON
BIN NUMBER : 22 1NST.NO. : ABIADUOS
CHROMATOGRAM NAME :
DONEBY: &
DATE : w\%\o< DATE :

Sample Information
Analysis Date & Time : 811 7/20053: 10:49 AM
User Name : Admin
Sample Name : QUMAPRIL
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATIOMQNNVALID\I
60805\QN-23.gcd
Instrument no : AHIADUO5
. --
0
-- --
10
_1 -- _
I
.
20
--- ---
min

BIN NUMBER : a3 1NST.NO. :AWADWOS
CHROMATOGRAM NAME :
DONE BY: (llf4
DATE : n IA\R\ a<

MRTl HEMTWARE LTD.
ACL W15r8N O F -TI INOUSTRfEB L W T E G
Sample Information
Analysis Date & Time : 8117/2005 3:48:09 A M
User Name : Admin
Data Name
Method Name
Instrument no
0 ..
,
0
. .. . -
-
--
- -
.
.
:I
L --
-. ..7
10
- - - r -
--
- . -
- --..
--- ,,- - ~
- --
. ..
20
-
, "
.-
A
min

PARAMETER : METHOD PRECISION
BIN NUMBER : $4 1NST.NO. :AH/ADWOS
CHROMATOGRAM NAME :
DONE BY:
DATE : ~\8\0<

QUINAPRU, HYDROCHLORIDE USP
7.4 LINEARITY & RANGE
Back to top
Page 20 of 82

i RESIDUAL SOLVENTS - ANALYTICAL METHOD VALIDATION 1
1 QUINAPRIL HYDROCHLORJDE USP 1
7.4 LINEARITY & RANGE:
The linearity studies for each solvent were carried out at different concentration
levels for n-Pentane, acetone, isopropyl alcohol (IPA), acetonitrile (ACN), di
isopropyl ether (DIPE), ethyl acetate and toluene from 20% to 150% of working
concentration.
The Regression curve was drawn and Coefficient of Correlation was calculated to
demonstrate the Linearity.
Acceptance Criteria for Linearity: - Correlation coefficient: NLT: 0.99
Based on linearity studies data as obtained above, compute the range for each
solvent (n-Pentane, acetone, isopropyl alcohol (JPA), acetonitrile JACN), di
isopropyl ether (DIPE), ethyl acetate and toluene), where the response would be
linear.
7.4.1. LINEARITY SOLUTIONS PREPARATION:

7.4.1.1 Blank: N,N dimethyl formamide was used as blank:
7.4.1.2 Diluent : N,N dimethyl formamide
7.4.1.3 Linearity solutions
TABLE - 7.4.1.3 - 1 - STOCK SOLUTION
2. Acetone I .OO 1.170 11,700

3. IPA 0.20 0.205 2050
5 100 rnl
4. ACN 0.08 0.08 1 810
(Lin A)
5. DlPE 0.15 0.160 1600
6. Ethyl acetate 1 .OO 1.050 10,500
7. Toluene 0.18 0.182 1820
Page 2 1 of 82

I RESIDUAL SOLWNTS - ANALYTICAL METHOD VALIDATION
I
TABLE - 7.4.1.3 - 2 - PREPARTION OF LINEARITY SOLUTIONS

Concentration in pprn Volume
of Lin A Final volume
Linearity levels n-
Acetone IPA ACN DIPE Toluene Solution with DMF
Pentane acetate in ml
Level- 1 (20%) 42 46.8 8.2 3.24 6.4 42 7.28 0.4 ml 100 ml
Level-2 (50%) 105 117 20.5 8.1 16 105 18.2 1.0 ml 100 ml
Level3 (80%) 168 187.2 32.8 12.96 25.6 168 29.12 1.6ml 100 ml
Level-4 (100%) 210 234 41 16.2 32 210 36.4 2.0 ml 100 ml
Level-5 (120%) 252 280.8 49.2 19.44 38.4 252 43.68 2.4 ml 100 ml
Level-6 (150%) 315 351 61.5 24.3 48 315 54.6 3.0 ml 100 ml
7.4.2 RESULTS:
Linearity Levels are injected and the areas as obtained are as follows;
TABLE - 7.4.2 -1
Level-] (20 %)
Injection Graph
Solvents n-pentane Acetone IPA D'PE Toluene
No- acetate NO.
I 2753688 205490 21689 8490 108061 145726 46278 25
I 2 2319944 186398 21354 7260 92254 142012 37876 26

3 2754400 206409 2 1971 8039 101697 133741 41307 27
Area
4 2800258 207060 15470 7670 11 1965 146217 40933 28
5 3623516 274152 20816 8069 140090 197710 44849 29
6 2904450 217863 19656 5827 113424 159830 51419 30
Average 2859376 216229 20159 7559 1 1 1249 154206 43777
SD 424879.592 30144.524 2438.1 82 944.33 1 16119.929 22923.664 4791.98 1
% RSD 14.86 13.94 12.09 12.49 14.49 14.87 10.95
Page 22 of 82

QUINAPRIL HYDROCHLORLDE USP
TABLE - 7.4.2 - 2
! Level-2 (50 %
' }
Injection EUlyl Graph
Solvents n-Pentane Acetone IPA acetate
Toluene No-
No.
1 7485191 546259 44672 18392 288912 381230 81391 31
Area
2 7486614 549735 44672 20096 294646 381230 78624 32
Average 7485903 547997 44672 19244 291779 381230 80008
TABLE - 7.4.2 - 3
TABLE - 7.4.2 4
Level-4 (100 %)
Injection Graph
Solvents n-Pentane Acetone IPA ACN DrPE Toluene
No. acetate No.
1 13327047 988968 99945 35 168 534837 693565 186854 35
Area
2 12201409 949478 99650 33366 498261 664203 168526 36
Average 12764228 969223 99798 34267 516549 678884 I77690
TABLE - 7.4.2 -5
Solvents
Injection
No.
n-Pentane Acetone IPA
I / / Emyl
acetate ( Toluene 1 Graph
No.
I 14650954 1 101726 1 1 8227 40478 579568 77908 1 198905 37

Area -
2 15615320 1220568 132519 43847 633365 869185 223457 38
Average 15133137 1161147 125373 42163 606467 824133 21 1181
Page 23 of 82

TABLE - 7.4.2 4
1 Level-6 (150 %)
Injection DIPE Toluene Graph
Solvents n-Pentane Acetone IPA acetate
No. NO.
1 20766482 1476391 142307 4995 1 8064 16 1022972 237950 39

1 Area -
823525 1013046 237656 40
2 21267483 1479909 136736 48961
Average 21016983 1478150 139522 49456 814971 1018009 237803
7.4.3 REGRESSION COEPFICIENT:
TABLE - 7.4.3 - 1
Conc. of Conc. Conc. of Mean
Mean Mean
Conc.of Mean
n- Area of Area of Area of ACN Area of
Linearity level Aceton
n-~entane Acetone IPA PPm I ~ A ACN
ppm
ppm e ppm
Level- l (20%) 42 2859377 47 216229 8 20159 3 7559
Level-2 (50%) 105 7485903 117 547997 21 44672 8 19244
Level-3 (80%) 168 11638280 187 883035 33 86123 13 30239
Level4 (100%) 210 12764228 234 969223 41 99798 16 34267
Level-5 (120%) 252 15 133 137 281 1161147 49 125373 19 42163
Level-6 (1 50%) 3 15 21016983 351 1478150 62 139522 24 49456
From graph (R') 0.9831 0.9919 0.982 1 0.992 1
Correlation 0.996 0.99f 0.996
0.992
coeffieient. (R)
Acceptance NLT 0.99
Criteria
Page 24 of 82

I RESIDUAL SOLVENTS - ANALYTICAL METHOD VALIDATION
i QUINAPRIL HYDROCHLORIDE USP
TABLE - 7.4.3 - 2
Of Mean Area
Conc. of Mean Conc. of Mean Area
Ethyl of
Linearity level DIPE Area Toluene of
acetate Ethyl
PPm DIPE PPm Toluene
ppm acetate
Level- 1 (20%) 6 112309 42 11 1249 7 43777
Level-2 (50%) 16 29 1 779 105 381230 18 80008
Level-3 (80%) 26 4678 1 8 168 619700 29 148453
Level-4 ( 100%) 32 516549 210 678884 -
36 177690
Level-5 (120%) 38 606467 252 824 133 44 211181
Level-6 (150%) 48 814971 315 1018009 55 237803
From graph ( R ~ ) 0.9886 0.9974 0.9826
Correlation coefficient. (R) 0.994 0.999 0.991
Acceptance Criteria NLT 0.99
R'= REGRESSION CO-OEFFICIENT WHICH IS CALCULATED ON GRAPH.

Correlation coefficient (R) = Square root of R~ which is calculated as above.
7.4.4 LINEARITY GRAPHS:

Graph 7.4.4-1
-- .. - - - - -- --
Linearity of n-Pentane
) 25000000 I
y=62575x+427645
RZ=09831 21016483
20000000
5000000
+ 2859377 .
I
I 0 t
0 50 100 150 200 250 300 350

Concentration m ppm
- -- - - --- - - --. . - - --- -
Page 25 of 82

QUINAF'RK HYDROCHLORIDE USP
Graph 7.4.4-2
Lineamity of Acetone
1600000
y = 4024 6x + 59776 1478150

1400000
R2 = O 9919
1200000
1000000 -
800000 -
600000 -
400000 -
200000 -
0
0 50 100 150 200 250 300 350 400
Concentrat1011In ppm
. - --- - - -
Graph 7.4.4-3
- -- - - - .--
Linearity of IPA
0 10 20 30 40 50
Concentration in ppm
Page 26 of 82

Graph 7.4.4-3
- - - -- -- .
. -- -
-
Linearity of ACN
10 'S 20
- --- - - --
Graph 7.4.4-4
-- --- - a - 7
Linearity of DIPE I
900000
1
10 20 30 40 50
Concentrat~onin ppm
- - -- --- - -- ...
Page 27 of 82

QWNAPRn, HYDROCHLORIDE USP
-
Graph 7.4.4-5
100 150 200 250

Concentration in p p m
.. -- .. . -- -- .- -
Graph 7.4.4-6
- -- -
Linearity of Toluene
300000 - I
I
y = 4 3 4 9 8x + 12597 I
25~00 R2 = 0.9826
' # 200000 -
i
' g "0000
,r:8 ,00000
' 50000 -
0
0 10 20 30 40 50 60
-
Page 28 of 82

RESIDUAL SOLVENTS - ANALYTICAL METHOD VALXDATION
QUINAPlUL HYDFtOCHLORlDEUSP
7.4.5 INFERENCE:

The coefficient of correlation was found to be more than 0.991.
7.4.6 CONCLUSION: Meets the acceptance criteria for linearity.
Sr. No. Graph No. Graph Name

Level- 1 (20% - 1)
Level- 1 (20% -2)
I 3 1 27 1 Level- 1 (20% -3) I
4 28 Level-1 (20% -4)
5 29 Level- l (20% -5)
6 30 Level-l (20% -6)
7 31 Level-1 (50% -1)
8 32 Level-1 (50% -2)
9 33 Level-l (80% -1)
12 36 Level- 1 (100% -2)

13 37 Level-1 (120% - 1)
14 38 Level-l (120% -2)
15 39 -
Level- 1 (1 50% 1)
Back to top
- -
Page 29 of 82

r PI Lr:i%tcJM QI: AliWTJ IMBGSTRIES LlMI~E;
Sample Information
Analvsis Date & Time : 811 712005 10:52:34 PM
usehame : Admin
Data Name : E:\GC-17 A\GC-~atai~~-VALIDATION\QN_VALID\I70805\QN-09.gcd
Method Name I SOlOS\DLL.gcm
: E:\GC-I 7 A\GC-Data\QN-VALIDATION\QN-VALID\
Instrument no : AHIADLIO5
min
Peak Table - Chamel I

- --
Peak# Ret.Tim_e_ Name - Area

- - Area%
8.858 N-PENTAW 2753688 83.7134
1
. .-.- - -- 10.20 8 .A-CEETO_N.E -
3 10.508 IPA - -
... 205490
- 2 1689 -
. 6.2470
0.6594
4 10.882 ACN - -8490 - - - 0.2581
-5
. 12.920 - DIPE
- - - - - -- 108061 3.285 1
6 14.194 ETHYL ACETATE-. - _14_5724 4.430
7 --19.706 TOL-ULNE 46278 1.4069
TO%! ... - . 3289422 100.0000 -
PRODUCT NAME :QIllNAPRlL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER : LINEARITY & RANGE
BIN NUMBER : INST.NO. :AWADWOS
CHROMATOGRAM NAME :
DONE BY: &
DATE : 24\%\6

Sample Information
Analysis Date & Time : 8/17/20051 1 :33:20 PM
User Name : Admin
Sample Name : QUINAPKIL
Data Name : Il:\GC- 17 A\GC-Data\QN-VALIDATION\QN-VALID\]
70805\QN-10.gcd
Method Name : t3:\GC- I 7 A\GC-METHODS\QUlNAPRIL.gcm
Instrument no : AHIADL:05
,
v l.
L\~-.'---, ,. .,.
... . .- .
min
Peak Table - Channel

Peak# Name- Are_a
1 N-PENTANE - . . 23 19944
2 ACETONE 186398
3 IPA - . .21354
-
4 ACN 7260
5 DlPE 92254
6 ETHYL ACETATE' i42012 .
7 . TOLUENE -.- 37826_-
Total -
2807398
PRODUCT NAME :QllINAPRIL HCL RESIDIJAL SOLVENTS VALIDATION

PAKAMETEK :LINEARITY &RANGE
BIN NUMBER : 2 " 1NST.NO. :AHIADLIOS
CHROMATOGRAM N A M E .
DONE BY: & ' ' O CHECKED B Y :
DATE : w\$log DATE : -

Sample Information
Analysis Date & Time : 8/18/200512:14:14 A M
User Name : Admin
Samvle ID : 20% STD 3
~ a t aName
'
Method Name
Instrument no
Intensity
-
500000 -- .
- -- -
rjj -
-
-- - .
I
i4
400000 '
45
I
' m
2
OD
- ...-. ~-
-- - --- . ~
---~-
- ~ p
- . -. . _
0 10 20
min
-- -. - - - Peak Table Channel 1 - .. -.

Peak# Ret.Time , Na-me -- Area -
Area% .
- 1 8.858 , NZPENTANE 2754403 84.2952
2 10.208 ACETDNE 206409 6.3169 --
-- 3 - 10.508 , IPA , - 21971 --- 0.6724
4 ,._10.882
.- tACN I - 8 0 3 L 0.2460
5 12.920 DlPE 101697 3.1 123
--
- - --
6
.- 14.194 ETHYL ACETATE1
. , -13374 1 .. 4.0930 - -
-.- 7 +- 19.706 TOLUENE- .- I 41307 -- - 1.264_2--- . :
Total
-- --3267567
- -- l00.0000
PRODUCT NAME :QUINAPRlL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :LINEARITY & RANGE
aNNuMBER: 27 1NST.NO. :AH/ADL/OS
CHROMATOCRAM NAME
d
D O BY:
DATE : 2418 105
: ao
DATE: *i 01;108

AARTI HEALTHCARE LTD.
BVZ DlYiSKSrV OF MR71 IHEIUSIRIES LlUiTEij
Sample Information
Analysis Date & Time : 8/18/200512:55:02AM
User Name : Admin
Data Name : E:\GC- 17 .4\GC-Data\QN-VALIDATION\QNNVALLID\I
70805\QN-12.gcd
Method Name : t3:\GC-17.4\GC-Data\QN~VALIDATION\QN~VAl.ID\180805\DLL.gcm
Instrument no A~I/ADL,'OS
Intensity
500000
400000
-~ - -
20
min
- -- -- --
Peak# Ret.Tirne Name Area Area%

1 8.845 N-PENTANE .2800_2_58. 84.1026. . .
2 10.193 ACETONE 207060 6.2 188
3 10.494 IPA 15470 0.4646
4 10.871 ACN .
. - 0 . . 0.2304
5 12.907 DIPE 1 1 1965 3.3627 -
6 14.171 ETHYL ACETATE' 146217 - 4.3915

7 19.691 TOLUENE .. 40933 1.2294.- -
Total 3329573 100.0000
PROD1lCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

BIN NCJMBER : 253 INST.NO. :AHIADWDS
CHRO%IATOCRAM NAME : QO'/- JC
DONE BY: & CHECKED BY :
DATE ; 2 4 \ ~ \ d !

Sample Information
Analysis Date & Time : 8/18/2005 1 :35:55 AM
User Name : Admin
Sample Name : QUTNAPRIL
Sample ID :20% STD 5
Data Name :E:\GC- 17 A\GC-Data\QN VALIDATION\QN-VALID\I 70805\QN-13 .gcd
Method Name : E:\GC- 17 A\GC-D~~~\QNIVAL~DAT~ONQN-VALID\~ 80805DLL.gcm
El
Et3 V
<
$
U
s e
6e s ii; ;
E 4
Om,
j2g ; =
'
00
- LA -- .& - -
.-. - -..-..
Peak Table
- -- - Channel
-
. -
1
.-
Peak# Ret.Ti_me,- ---Nam-e Area -- Area_%---
I +8.918 ,N-PENLANE- . 3 6 2 3 5 1 6 84.0879 -
2 10.262 A-CETONE: 274 152 6.3620
- 3 _ ~ O . ~ ~ B J P A - ~ 20_8i6 0.4831- --
4 10.935:ACN
, 8069 .. 0.1872 - -
- 5 12.977 4DIPE 32509
140090 -
-
6_-
. 14.255 /ETHYL ACET~T E-.-~~~~~O
4.588_1
-
- - - -
7 - 19,27 1 ! TOLUENE- .
.- . 44849
1.0408
.- , --
Total 2 -- A
--- 4309202
100.0000 - . -

I PARAMETER :LINEARLTY & RANGE
BINNUMBER: &q INST.NO. :A W A D M S
CHROMATOGRAM NAME : 1 0-1. cdr
DATE: ~ \ 8 \ 0 f DATE :

Sample Information
User Name : Admin
S a r n ~ l eName : QUINAPRIL
sample ID
Data Name
Method Name . - -
Intensity
500000
400000
.-. .
.
20
min
. Peak Table - Channel 1

Peak# Ret.Time Nane - Area - Areayo
1 8.9 12 N-PENTANE 2904450 83.6422
2 10.264 ACETONE - 217863. .- 6.2740 -
3 10.5_65. IPA - - 19656 .. 0.5660

4 10.940 ACN . 5827 0.1678
5 12.987 DlPE 1 13424 3.2664
6 14.263 ETHYL ACETATE 159830 4.6028 . _
7 19.809 TOLUENE 5 14J9 1.4808
Total 3472469 . 100.0000
PRODUCT NAME :QlllNAPRlL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER : LINEARI'I'Y & RANGE
BIN NUMBER : %
, o 1NST.NO. :AH/ADWOS
CHROMATOGRAM XAME : 07~1.~
DATE: U\S\OC DATE :

Sample information
Analysis Date & Time : 8/18/2005 3: 1459 AM
User Name : Admin
Samule Name : OUINAPRIL
~ a m p ~I De : 5'0% STD I
Data Name : E:\GC- 1 7 A\GC-Data\QN-VALIDATION\QN-VALID\
I70805\QN-I 5 .gcd
Method Name : E:\GC- 17 A\GC-METWODS\QUINAPRIL.gcm -
Instrument no : AIf!ADL/O5
Intensity
500000
400000
--
20
rnin
Peak Tw Channel 1
Peak# Ret.Time Name -Area
- Area%
1 8.965 N-PENTANE 7485191 84.6162
2 10.336 IPA 546259 . 6.1752 . -
3 10.659 IPA -.. 44672 - - 0.5050- -
4 11.003 ACN 18392
- 0.2079
5 13.059 DIPE 288912. . 3.2660 -
6 14.328 ETHYL ACETATE. 38,230 4.3096

7 19.804 TOLUENE 81391 _ 0.920 1
Total 8846047 . 100.0000 -
- .. -
PRODUCT NA.ME : QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

B1N NUMBER : 31 1NST.NO. : AWADWOS
CHROMATOGRAM N A M E .
DATE :

Sample Information
User Name : Admin
Samole Name : QUINAPRIL
sample ID : 50% STD 2
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATION\QN-VAL,ID\I
70805\QN-16.gcd
Intensity .-
500000 -- -
20
min

PARAMETER :LINEARITY & RANGE
BIN NUMBER : 3% INST.NO. : AHIADWOS
CHROMATOGRAM NAME :
DONEBY: CI-lEC
DATE : 24\8\Cd

Sample Information
Analysis Date & Time : 8/18/2005 4:35:08 A M
User Name : Admin
Samole Name :OUINAPRIL
sample ID
Data Name
Method Name
Instrument no
Intensity
500000
- --- . .
. .
20
min
- -- -- Peak Table - Channel 1---

--
Peak# I Ret.Tirne 1 - . - . - N a m e _ --- Area
_. -
1 8.919 N-PENLAKE 12980437

-- .
2 -
. 10.265 ACETOE- . , 992252
3--, 10.575 IPA- -4 90830 -
- 4 -r 10.944JdX I 30138
-
5 12.989IDIPE - 5268 15
6
--
14.263 IETHYL A m A T E 491615 -
7 , 19.745 !TOLmN-E ; - 1 6 4 3 2 L --
Total I -15482475
-
I -
PRODUCT NAME : QUlNAPRIL HCL RESIDUAL SOLVENTS VALIDATION

BIN NUMBER : 33 INST-NO. :AH/ADLWS
CHROMATOCRAM NAME : SO*/. u ( < ~ e
DONEBY: CHECKEDB
DATE : 24)%\0< DATE :
- -p - -

RPI L'i\'iSIBhi ewi AARn IIBUSTR!ES LIMITED
Sample Information
Analysis Date & Time : 8/18/2005 5: 1 5 5 4 AM
User Name :Admin
Sample Name : QUINAPREL
Data Name : E:\C;C-I7 A\GC-Data\QN~VALlDATIOMQN~VALID\170805\QN~18.gcd
Method Name : E:\CiC- 17 A\GC-METHODS\QUINAPRIL.gcrn
lnstrumcnt no : Atl'ADL,'O5
Intensity
500000
L -
- -.
10 20
min
Peak Table Channel I -

Peak# Name Area
1 N-PENTANE 10296 122
2 ACETONE 7738 18
3 I PA 81416
4 ACN 30339
5 DlPE 408821
6 ETHYL ACE TAT^ - . 541724
7 TOLUENE 132578
Total 12264818

PARAMETER : I.INEARI'TY & RANGE
BIN Kl'MBER : 39 1NST.NO. :AHfADWOS
CHROMATOGRAM NAME :
W W E BY:
DATE : 24\$?.\0( DATE :

AARf l HEALWARE LTD.
-.r .Nu#Ol?i 8%PAR I?IWOUSWIES LlMm9
Sample Information
User Name : Admin
Data Name : E:\GC-17 A\GC-Data\QN-VALIDATION\QN-VAL,ID\I
70805\QN-19.gcd
Mrthod Name : E:\GC-17 A\GC-METHODS\QUTNAPRIL.gcm
Instrument no : PJ1IADWO5
20
min
Peak Table - Channel f

-
Peak# Ret.Tirne Name .
1 8.811 N-PENTANE .-
2 10.156 ACETONE
3 10.465- IPA .
4 10.833 -ACN
5 12.867 DlPE
6 14.140 ETHYLACETATE-
7 19.668 TOLUENE
Total

BIN NUMBER : 3 < INST.NO. :AH/ADL/OS
CHROMATOGRAM NAME :>o'/ Jt~al
DATE : DATE :

AARn HEALTHCARE LID.
,aebi 41vr9in)h OI GRTI I N I K ; ~ ~ L
E ~SM F E : ~
Sample Information
Analysis Date & T i m e : 8/18/2005 6:37:35AM
User Name
~ ~ : Admin
Data Name : E:\GC- I7 A\GC-Data\QN VALIDATION\QN VALID\ I70805\QN-20.gcd
Method Name : E:\GC- I 7 A\GC-METHO~~S\QUINAPRIL.~CI-~~
Instrument no : AH/ADL/OS
Intensity . . .- --
500000 -
w
Z
2
3
4.
400000 F
P
Lb
- ~
. - -- -~ - ~ - .- - - . . .. . .. . . 7--- - --.
0 10 20
min
Peak Table --Channel 1

- -
7
Total
PRODUCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALlDATION I

BIN NUMBER : 3 INST.NO. :AHIADUOS
CHROMATOCRAM NAME :
DATE :

Sample Information
User Name : Admin
Data Name : E:\GC- I7 A\GC-Data\QN VALIDATIOMQN-VALID\I 70805\QN-2 1 .gcd
Method Name : E:\C;C-17 A\GC-METHODS\QUINAPRIL.~~~
Intensity -- -.
500000
400000
300000
200000
100000
- - . .-
20
rnin
-
Peak Table - Channel I-
peak# ~et.=& N-me-. - Area --
I n 793 N-PENTANE- - 14650954

I# ACETONE- -. 11W26 --
.lv.4EL ]PA. . - - 1 18227

a
, A""
- -
4U4-13
5 , -1_2.855 DIPE -
579568
6 14.126 _ET_HYL _ACETATE 279081..
hC
-
PRODUCT NAME :QUlNAPRIL HCL RESIDUAL SOLVENTS VALIDATION

BIN NUMBER : 31 1NST.NO. : A W A D M S
CHROMATOGRAM NAME.
DONEBY: _&-
DATE : w\8\05

Sample Information
User Name : Admin
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATION\QN-VALID\
170805\QN_22.gcd
Instrument no : AHIADUOS
Intensity
500000
400000
300000
20
min

--
Pea&& ,~et.~i&-- N-i!-. Area

1 _ - - .8.798
--. ~-JENTANE - -- 15615320
2 10,143 LACETONE_-- 1220568_..-._
3 10.452 IM - - - - 1 325L9- -.
4 10.822 , ACN - - 43 847
5 --12.855 , DIPE . 633365 --- -
6 14.121. ETHYL.ACETATEE
- --- W!85
.- 7 1 9 . 6 a TOLU-ENL - - 223457 --
Total - . - -- 18738261

PARAMETER :LINEARITY 8: RANGE
BIN NUMBER : 36 1NST.NO. : AH/ADUOS
DATE : DATE :
- -

a /wm HEUTHCARE LTD.
{**I dIVIYI(SN (3$ M R l i IRIWSWtES LMA1ITEr)
Sample Information
Analysis Date & Time : 81 1812005 8:40:00 AM
User Name : Admin
Sample Name : QUWAPRIL
Data Name : E:\GC-17 A\GC-Data\QN-VALIDATION\QN-VALID\
I 70805\QNA23.gcd
Method Name : E:\GC-17 A\GC-METNODS\QUINAPRfl.gcm
Instrument no : AWADUOS
- ---
20
min
-
Peak
- 7
-
Table Channel 1
Pea@ R&.Time Name -- Area
1 - 8.798 N-PENTAN&. 20766482 -
2 , 10.146 ACETONE - 1476391.

3 -10.455 IPA -- 14307 __
4 10.826 ACN
--- -- . L . 49951
5 12.859 DIPE - 806416 -
6- 14. L
X .ETHYLACETATE---- 1022972 -
7 19.659 TOL-UZNE
-- - 237950
T~td.. . -- 24502469
PRODIJCT NAME : QUlNAPRlL HCL RESIDUAL SOLVENTS VALIDATION

BIN NUMBER : 3q INST.NO. : AH/ADL/OS
CHROMATOGRAM NAME :
DONEBY: & CHECKED BY :
DATE : 24\ d o < DATE :

AARTf HEALTHCARE LTD.
%s+l fKvlBlC)N Of: M R T f INEM3LCfRfES ktMlV.n
Sample Information
User Name : Admin
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATiON\QN-VALID\I
70805\QN-24.gcd
Method Name : E:\GC- I7 A\GC-METHODS\QUINAPRLL.gcrn
Intensity
500000
. - -
20
min
. --
Peak# Ret.Time Name Area
1 . 8.808 N - P E ~ A N E - .- 7 2 E67483
2 -10.156
- , ACETaNE 1 1479409 .-
-3 10.465 , IPA 1 136736 -
4 - 10.82y,ACN --- -. 48961 ....
5 12.867 DIPE 823525 --

6 14.140
- - .ETHYLACE~~T . ~.' l(ll3046
2 -- 19.670 TOLUENEE-- - 237636 _ .

Total A- .- - . --- 250073 16

BIN NUMBER : 40 INST.NO. :AH/ADL/OS
CHROMATOGRAM NAME :
DONE BY: CHEC
DATE : ~ \ g \ d <

. --
QUINAPRa HYDROCHLORIDE USP
7.5 LIMIT OF DETECTION

&
LIMIT OF QUANTITATION
Back to top
Page 30 of 82

1 QUINAPRIL HYDROCHLOFUDE USP 1
7.5.1 LOD & LOQ:
LOD and LOQ can be calculated based on the standard deviation of the response and slope
as follows;
I0 a
LOQ =
S
Where;
o is the standard deviation of the response
S is the slope obtained from the calibration curve
TABLE - 7.5.1 - 1
For n-Pentane
S 62575
c 427563
Concentration in prn Observed Area Theoretical Area Difference
42 2859377 30557 13 -196337
105 7485903 6997938 487965
168 1 1638280 109401 63 6981 17
210 12764228 13568313 -804085
252 15133137 161 96463 - 1063326
3 15 21016983 20138688 878295
D 8 13958
LOD in pprn 43
LOQ in ppm 130
L
Page 3 1 of 82

I
TA3LE - 7.5.1 - 2
For Acetone
S 4024.6
c 59776
Concentration in pm Observed Area Theoretical Area Difference
47 2 16229 248 127.28 -3 1898
117 547997 530654.2 17343
187 883035 813181.12 69854
234 969223 1001532.4 -32309
28 1 1161 147 1189883.68 -28737
35 1 1478150 1472410.6 5739
o 40250 -
LOD in ppm 33
LOQ in ppm 100
TABLE - 7.5.1 - 3
For IPA
S 2363.8
c 1946.7
8 20 159 21330 -1 171
21 44672 50405 -5733
33 86 123 79479 6644
41 99798 98863 935
49 125373 1 18246 7127
62 139522 147320 -7799
0 6178
LOD in ppm 9
LOQ in ppm 26
Page 32 of 82

r
QULNAPRIL HYDROCHLORIDE USP
TABLE - 7.5.1 4
For ACN
7
S 1986.8
c 2593.3
3 7559 903 1 -1472
8 19244 18686 558
13 30239 28342 1197
-
16 34267 34779 -512

19 42 163 41217 946
24 49456 50873 -1417
0 1359
LOD in pprn 2
LOQ in ppm 7
TABLE - 7.5.1 -5
For DIPE
S 161 15
c 21388
6 1 12309 124524 -12215
16 29 1779 279228 12551
26 46781 8 433932 33886
32 5 16549 537068 -205 19
38 606467 640204 -33738
48 814971 794908 20063
(3 26141
LOD in ppm 5
LOQ in ppm 16
Page 33 of 82

I
TABLE - 7.5.1 4
For Ethyl acetate
S 3228
c 18040
42 11 1249 153616 -42367
105 381230 356980 24?50
168 6 1 9700 560344 59356
210 678884 695920 -17036
252 824133 83 1496 -7363
315 1018009 1034860 -16851
0 36151
LOD in ppm 37
LOQ in ppm 112
TABLE - 7.5.1 -7
For Toluene
S 4349.8
c 12597
Concentration in pm Observed Area Theoretical Area Diffc rence
7 43777 44264 -487
18 80008 91763 -1 1756
29 148453 139263 9190
36 177690 170930 6760
44 21 1181 202596 8585
55 237803 250096 - 12293
0 9934
LOD in ppm 8
LOQ in pprn 23
. - - - - - -
Page 34 of 82

I RESIDUAL SOLVENTS - ANALYTICAL METHOD VALLDATION I
1 OULNAF'lUL HYDROCHLORIDE USP I
7.5.2 LOD & LOQ SOLUTIONS PREPARATION:
7.5.2.1 Blank N,N dimethyl formamide was used as blank

7.5.2.2 Diluent N,N dimethyl formamide
7.5.2.3 LOD & LOQ solutions:
TABLE - 7.5.2.3 - 1 - STOCK SOLUTION
5. DIPE 0.15 0.160 1600

6. Ethyl acetate 1 .OO 1.050 10,500
7. Toluene 0.18 0.1 82 1820
TABLE - 752.3 - 2 - PREPARTION OF LOD SOLUTIONS
LOD 21.00 23.40 4.10 1.62 3.20 2 1 .OO 3.64 0.2 ml 100 rnl
-- -
LoQ 42.00 46.80 8.20 3.24 6.40 42.00 7.28 0.4 ml I00 rnl
7.5.3 RESULTS:
I
Page 35 of 82

TABLE - 7.5.3 - 1
1 LOD (10% STD)
(
Solvents InJeaion
No. / 1
n-Pentane Acetone IPA 1 I Toluene I Graph
No.
- - --
3 1290374 114681 11760 4016 57076 86560 10238 45
Area
4 1460491 123422 14595 3565 66719 86675 12761 46
5 1167972 99002 10980 351 7 56462 78324 12451 47

6 1749627 140354 10694 4399 63867 89143 9822 48
Average 1420874 119067 12802 4026 59088 84511 12058
TABLE - 7.5.3 - 2
1
LOQ (20% STD) 1

1
Solvents InJenion
No, I
n-pentane I Acetone I IPA 1 Ethyl / Toluene 1 Graph
1 2753688 205490 21689 8490 108061 145726 46278 49

2 2319944 186398 21354 7260 92254 142012 37876 50
3 2754403 206409 21971 8039 101697 133741 41307 51
Area
4 2800258 207060 15470 7670 11 1965 146217 40933 52
5 3623516 274152 20816 8069 140090 197710 44849 53
6 2904450 217863 19656 5827 113424 159830 51419 54
Average 2859377 216229 20159 7559 1 1 1249 154206 43777
SD 424879.444 30144.524 2438.182 944.331 16119.929 22923.664 4791.98 1
% RSD 14.86 13.94 12.09 12.49 14.49 14.87 10.95
------ -. -
Page 36 of 82

7.5.4 OBSERVATION:
The LOD levels for each solvent are as follows;
TABLE - 7.5.4 -1
Solvents nBentane Acetone IPA ACN DIPE Ethyl acetate Toluene
Calculated ppm 43 33 9 2 5 37 8
Observed ppm 21 .OO 23.40 4.10 1.62 3.20 2 1 .OO 3.64
The LOQ levels for each solvent are as follows;
TABLE - 7.5.4 - 2
-
Solvents n-Pentane Acetone IPA ACN DIPE Ethyl acetate Toluene

Calculated ppm 130 100 26 7 16 112 23
Observed ppm 42.00 46.80 8.20 3.24 6.40 42 .00 7.28
7.5.5 INFERENCE:

The LOD and LOQ are well below the internal limit.
7.5.6 CONCLUSION: Meets the acceptance criteria for LOD & LOQ.
- - - - -
Page 37 of 82

QUINAPRIL HYDROCHLORlDE USP
Back to top
Page 38 of 82

ii sfL)IV&QN OF 4baRf S BkDUS7RBS iWIGFlj
Sample Information
Analysis Date & Time : 8/17/20055:26:01 PM
User Name : Admin
Sample ID : BLANK
Data Name : E:\GC- I7 A\GC-Data\QN-VALIDATION\QNNVALID\I
70805\~~-0
1 .gcd
lnstrurnent no :AWADWOS
... .. . .
0 - - - ~.- .,.> 5
.. .
--
> - >
- .-- . -- - -- - - - -
, - __-, _ _ _ . ....- -.
0 10 20
min
II PRODUCT NAME : Q U l M I R l L HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :M D
11
BIN NUMBER : 41 INST.NO. :AB/ADL/OS
CHROMATOGRAM NAME :
DATE :rLU\S\& DATE :

AARR HEALTHCARE LTD.
) ~Am'n O?3BWSm$E$
n$i~ v j b i rOP t MITEG
Sample Information
Analysis Date & Time : 8/17/2005 6:06:52PM
User Name : Admin
Sample ID : BLANK
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATION\QN-VALID\I
70805\QN-02.gcd
Instrument no :AH/ADUO5
Intensity
500000- -
-. - -.. . --r-7- --~- .- -- ~ - -

. -. . -- ,--- . -i
0 10 20
min
PRODUCT N A M E :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :LOD
BIN NUMBER: 42- 1NST.NO. :AH/ADL/O.C
,
CHROMATOGRAM NAME :
DONE BY: &- CHECKED BY :
DATE : %u\&< DATE :

Sample Information
User Name : Admin
Samnle Name : OUINAPRIL
sam;r~e ID : io% sTD I
: E:\GC- 17 A\GC-Data\QN-VALIDATION\QN-VALID\]
70805\QN-03.gcd
Data Name
Method Name : E:\GC-I 7 A\GC-METHODS\QUTNAPRIL.gcm
Intensity -- - -- -- --
500000--- -
- -- ppL 7-
m
I W
I t.
200000- 2W
W
W U
3 u G *?
Fi 2
100000 1 E.282 s v
' s
8
: '
I,,
!
\
1 z2 - a w
g ::
N P 1 "<I-*'?-, ,
2 z z =
,
0 --- -- -
__ _ ._-A-
OP
-
1 i . - -
-- - -1-- - - - - .---
. - -
0 10 20
min

- -- I-
-- ~eak#~et.E Name -- ] A m Area% --,

1 .8.910 N-PENLANE 129598_0_- ..- 82.5878 --
--
.
2 . , 10.262 ~ E T O N E 1 0 7 9 2 1 .
-
- - 6.873 --
. ' 3 10.552 IPA - , - 14657 --, 0.9340

4 ,10.938 ACN _ .--4538 + - 0.2892
- 5- 12.968 DIPE -- -51828 - - 3.3028
6 14.242 E T H Y L A C E T A T E / 8 0 7 7 - 5.1444 -_
7 19.751 ---
TOLUENE- 13566- 0.86G
lOO.O_o_oO_
-
Total -. .
1569X-- --

PARAMETER :LOD
BIN NUMBER : 613 1NST.NO. :AUIADWOS
CHROMATOGRAMNAME: to/.J c ~ r
DATE: SLI \8\9< DATE :

AARTI HEALWARE LTD.
RPI DlVISfUN C2$ A A R n INOUSIRIES LlMITEb
Sample information
User Name : Admin
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATION\QNNVALID\l
70805\QN-04.gcd
Method Name : E:\GC-I 7 A\GC-METHODS\QUWAPML.gcm
Intensity
500000 -
min
-- --
Peak Table - Channel
.
-- -
Peak# ' Ret.Time NanL ,Area 7

~rea% - -
. 1 , 8.941 N,PEN_TANE -_ j 1 5 6 0 8 0 2 - 83.6535 - '

.-. 2 1 2 8 5 ,ACETONEL 1. A2%02-2- -- 6.9151
3-
. 10.595IPA _ 14123 - - -
- 0.7569 .
4--
10.963 ACN - - -4121- - -
0.2209-
58518. --
5
6
-- 7 -
13.005DIPE
~~.~~~.EEYLACETATE-
-
85637
-
,
3,1396-
4.5898-
0.7241
-
- -,
- - 7 , 19.820 I T O L U E X + 1 3 a --
-- Total -
I -
1865794
- - -- 100.0000

PARAMETER :LOD
B M NUMBER : 44 1NST.NO. : AHlADWOS
DATE :

Sample Information
User Name : Admin
S a m ~ l eName : OUWAPRIL
sample ID : lb% STD 3
Data Name : E:\GC-17 A\GC-Data\QN VALIDATION\QNVALID\170805\QN-05.gcd
Method Name : E:\GC-17 A\GC-METHo~S\QUINAPRIL.~~~
Intensity ---- - - -- - - -- -
500000 --
-- - -
20
min
- - --- ---- ---- Table - Channel I-_

Peak _ -
Peak#Ret.Time ; Name -- , Area ~ r & / o --
. 1 8.955 1 N - P E N T A N E -,
+-
1290374 + - - 81.9439-
2 --10.298 ,ACET_OrJE
- A
114681. -.1
-- 7.2827
3 10.606 IPA
,
4- 11760
-
-
, 0.7468
4 -10.977 , A m - . .
- 4_016-- -- 0.2550 - ...
5
-- -.13.013 _DIPE 5?o?6 - 3.6245
6 , ~~.~&-ETHYL_AcETK!%- 86560 - - 5.4969 -
.
.-.
.7
- - 19.798 ,TO=-
- l023L.
I --1374701-
-- 0.6501
Total
-
- - - -
-- - 100.0000- -- '
PRODUCT NAME :QUlNAPRlL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :LOD
BlN NUMBER : 1NST.NO. :AHIADWOS
CHROMATOCRAM NAME : to'/. JCUe 1 3 +

,
DATE : DATE :

Sample Information
User Name : Admin
Samnle Name : OUMAPRIL
Sam& ID : CO%STD 4
Data Name :E:\GC-17 A\GC-Data\QN-VALIDATIOMQNNV~ID\170805\QN-06,gcd
Method Name :E:\GC-17 A\GC-METHODS\QUMAPRIL.gcrn
Intensity . . -
500000 -
-
I
- - .--. , --- . -- - -- -- -
-. -- - -
0 10 20
rnin
.- -- .
Peak
-
Table - C b e l 1
.
- ----
Peak# Ret.Time . .--N w e P C

- a- -_
- 1 8.954 N-PENTANE
- ! _1460491
, --
2 ,
3
1 10.990 , G C N
-- -
4 3 5 6 5
p- 5 -- 13,016 IDIPE - 66719. +
6
- P
7 +- 19.798 TOLUENE- 12761

-Tot&- A 1768228
--
PRODUCT NAME ;QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :LOD
BIN NUMBER ; 46 INST.NO. :AWADWOS
DATE : DATE :

AARl7 HEALWARE LTD.
A*# W l t E t D M OI: A A R f r IWWS7RiES LlMlTFEt
Sample Information
Analysis Date & Time : 811 7/2005 9:30:58 PM
User Name : Admin
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATIOMQN_VALID\I
70805\QN-07.gcd
Method Name : E:\GC- I7 A\GC-METHODS\QUMAPRIL.gcm
Instrument no : AWADLt05
400000 -
W
Z
2
300000 Zi
$ I
I
z
01 W i
200000
00
I 2
C
U W
W
Z
0
u
>
2 G3 ,",
100000-
1 ' s
225 k 2 F
=
g , ,
I
* I
me.
m,, N
L
P-
O ,
' 1
*.
' -"-d.-+
228 8 " m
-
i
-.
I -0,
- --
n f
0 --
0
-
- --
- _ -.
_ _
- --.
-
-- 7
-
-
-____
A - -
- n - - - -
10
._ - -
20
r. _ -_ _--
min
--
Pe$ Table - Channel _i -
-
-
- . - . -
.-
&ak# Ret.Time we- Area -__-*.. Area!% - -
-_
--
1 8.986 ,N-PENTANE 1 -!167972- 81.1502 -
-.
12
3- .
10.332 ACETONE - - - -- 99002-
10,639 ,IPA_.. -- - 10980
- 6.92%
0.7486
-
0.2462
-
- - --
- -
- ,
-- 4 1 11.030 I A C N - - ~ - - - -3517 -
5
-. , 13.032 I DEE -- 56462- , - 3.9520 -
--
6 . 1 4 . 3 0 6 AC~ETA-!~ ~ ~ ~ - 78324 5.4821 -- -
7 19.784 TmWENE , -1 2 4 5 1
- - 0.8715-- +
--
TotL -. -- -
1428708-- --
100.0000
- - - _-
I PRODUCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION 1

PARAMETER :LOD
BMNUMBER: 47 INST.NO. :AHIADWOS
DATE : M\R\Q< DATE :

AARTl HEALTHCARE LfD.
5 or
pi I ) ~ V I ~ ~ U N 1~ f f ~MWISTRES L*IIT&>
Sample Information
Analysis Date & Time : 8/ 17/2005 10: 1 1 :41 PM
User Name : Admin
Data Name :E:\GC- 17 A\GC-Data\QN-VALIDATIONQN-VALID\
17O805\QNdO8.gcd
Method Name : E:\GC-17 A\GC-METHODS\QUWAPRIL.gcm
lnstrument no : AWADLIOS
Intensity
500000
- -
20
min
Peak Table - Channel I_

-
-
Peak# 1Ret.Tirne'
I 8.946 tN-PENT&
-
. .&mK
-- --
*EiL
-
1749627
-- Area%_
84.6087
.- .
--
.
A-
2-. - 10.289 , ACETONE t>TB - - 6.7873L -

3 10.599 IPA --
-- 10694 -
- - 0.51.71 - -
4 - 10.943 ,ACN 4399 0.2127

5 -13.010 , _ D L P E
- -
.
-
+
A
-63867
-
-
---
--
- 3.0885
4.3 108
--
-7
1
6
.- - 14.283 I ETHYLACETATL 8 9 1 4 3
7 19.797 TOLU-ENE 1---
-- 9822 . 0.4750 ..
Total A- .- ..2061906- 100.0000 - -

PARAMETER : LOD
BIN NUMBER : 4 INST.NO. :AHJADWOS
CHROMATOGRAM NAME :
DATE : DATE :

Sample Information
User Name :Admin
Data Name : E:\GC- 17 A\GC-Data\QN VALlDATlOMQN VALID\170805\QN 09.gcd
Method Name : E:\GC-17 A\GC-~ata\~~-VALIDATION\QN~VALID\I
80805D~i.~crn
Intensity
500000 - -- -- -
.... --- --- -

20
min
--- -- - -
Peak Table - Channel l - . - -
Peak# &Time-
--- Name Area --
~ r e g -!
-
.--
.1...- 8.858 , N:P_ENTANE- 2753688 .. 83.7134---
2 10.208 ACETaNE . . 2!&l% -- 6.2470
3 -10.508 -1PA , 21689 - 0.6594
4 , 10.882 ACN- 7- 8490 0.2581
.._ 1
. 5 -12.9200DLPE - - -108061
- 3.2851
- .A
6 14.194, ETHYL- ACETATIT MTXL -- - -- . 4.4301 -*
--
7 , 19.706 TOLUENE_- L4 6 2 7 8 -- - 1.4069-
Total -
I -
-
3289422 _- 100.0000 - -
I PRODUCT NAME : QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

I PARAMETER :LOQ
BIN NUMBER : 4 1NST.NO. : AHIADIAS
CHROMATOGRAM NAME '
N BY: &
DATE : 3.4) B ~ O C DATE :

Sample Information
Analysis Date & Time : 8117/2005 1 1:33:20 PM
User Name : Admin
~ a m b ID
~e : 50% STD 2
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATION\QN-VALID\I
70805\QN-10.gcd
Intensity
500000
400000-
300000
--
Peak Table - C&gnel-l- _ - -. -
Peak# ;~et.~irne-' Name 7 Area Area%_
1
. --- I 8.895 IN~PENTANE
2 ~ A C E T O N E
- -- I
1 2319944 -
186398 -
82.6456
6.6402
3 1 10.550 ;1I + 21354 - ---- 0.7607 1
4 ! 10.933 (ACN- 7260 + - -0.2586- 4
5 12.990 DIPE- 9254 3.2865 --
- 6 - 14.280 ETHYLACETATE-
-- 142012 -' 5.0590 --
-7- 19.835 TOLUENE . 37876-

- -
- 1.3_493----
Total - . - -2807098-. - . . 100.0090- _
.

PARAMETER : LOQ
BIN NUMBER : ,<0 MST.NO. :AHlADW05

Sample Information
User Name :Admin
Data Name 170805\QN- 1 1.gcd
: E:\GC-I 7 A\GC-Dsta\QN4VALIDATION\QNNVALID\
Method Name : E:\GC-17 A\GC-Data\QN-VALIDATIOMQNNVALID\i80805U)LL.gcm
lnstrument no : AHIADLIOS
Intensity -..
500000 --
7 W
Z
I
14
' ?
I ee
2
00
min
--
Peak Table - -
- --
Channel
- I
1
P&# TRet.Time N a m e Area
1 8.858 N-PEKTANE , .-2754403 ---
2
- 10.208 ACETO--.. , 2.06409__ .
3. 10,508 I P A - 21971 --
4 ,10.882 ACN .--.-

- 8039 --
-- 5 , 12.920 DIPE
- 101697-p
6 , 14.194 ,THYL ACDATE! -m41
7 ! 1 9 J K TOLUENE I 41307 .- - .
- Total - -
-- - L-3267567-
- ---

I PARAMETER :LOQ
I

Sample Information
Analysis Date & Time : 8/18/2005I2:55:02
AM
User Name : Admin
: f ~ STD
h 4
: E:\GC-17 A\GC-Data\QN-VALIDATIObAQN-VALID\I
70805\QN-l2.gcd
Method Name : E:\GC-I 7 A\GC-Data\QN-VALIDATION\QNNVALID\l
80805U)LL.gcm
Intensity
500000
-. - ----- -- -
-.... . - -
.. . . ..-. . -.
. .. .
0 10 20
min
. --
-
Peak Table Channel I _
Peak#
- -- Ret.Time K~ame _- Area -- _,
.-- 1 8.845 N-PENTANE 2800258 --,
2 - 10.193 .ACETONE 207060
--
3 . 4 9 4 - rse ..
1 0 - . -- - 15470
- -
4 - 10.871 A C N -.- - - 7670 -
5-- 12.9!JT-DIPEp- 11 1965

6 14.171 E T H Y L A & T ~ - - - ~146211 -
--7 _ -19.691 _ T O L U N E 40933
Total , - - 3329573
-- . --

PARAMETER :L O Q
BIN NUMBER : 52, INST-NO. :AWADLIOS
CHROMATOGRAM NAME :
DATE : U l \Q 104 DATE :

Sample Information
Analysis Date & Time : 8/18/20051:35:55 AM
User Name : Admin
Sample Name : QUINAF'RIL
Data Name : E:\GC-17 A\GC-Data\QN VALIDATION\QN VALID\170805\QN-13 .gcd
Method Name : E:\GC-17 A\Gc-D~~~\QN~VAL~DATION\QN~ALID\I 80805WLL.gcm
Intensity
500000-
20
min
Peak Table - Channel I -

"--
- -I - --r---& --
peak# ,Ret.Time~ Name_,_ . 2 Area% -
1 p 9 1 8 NZENTANE -- 362312_6 84.0879 --
2
3
, 10.262 ~ACETONE
,10.558 IPA - -
-
-- -
-1-mL-
20816
_.
- - 6.3620
0,4831-
-
- -
7 10.935 ACE 8069

- -1- -- 0.1872
3.2509
--I
5 .-_12.977 ,DIE 140090
-
--
- .--
-
- 6
-7 +
- .14.255
- _ E ~ ~ ~ ~ L ~ ~ ~ ~ -~ ~ $ 14,5881
19.771 TOLUENE 44849
. 9 7- _ 7 1 0
-- 1 . 0 ~ ~
Totla- - - - 4309202 --
-- l000000 .
-
I PRODUCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :LOQ
BIN NUMBER : $3 INST.NO. :AWADLI05
CHROMATOGRAM NAME :
DATE :

Sample Information
User Name : Admin
Sample Name : QUDJAPRIL
Data Name : E:\GC-17 A\GC-Data\QN-VALIDATION\QN-VALID\]
70805\QN-I4.gcd
Method Name : E:\GC-1 7 A\GC-Data\QN-VALIDATION\QN-VALID\18080S\DLL.gcm
-- - -- - - - - - - - -- - - - -
0 10 20
min
-
Pgtk Table Channel I
_
Peak# Ret.Time Name Area --
1 -- 8.912 N-PENTANE -
- 2904450 -
2
-- -101264 .A C E S Q E N L _---- 217863
- _
3 1 0 X I P A ---- 19656 -.--, . .
-- -4 -10.940 ACN -- 5827
- _ - ...
5 12.987 DIPE - 1 13424
6 -14263 ETHYLACE==.- - 159830 -- - -
7 19.809 ,'JOLU-ENE 51419

- Total L
- - - - 3 4 n 4 6 9
I PRODUCT NAME : QUINAPRIL HCL RESIDUAL SOLVEMS VALIDATION

PARAMETER :LOQ
BIN NUMBER : 54 1
MST.NO. : AHIADWOS

QUINAPRZL HYDROCHLORIDE USP 1
ACCURACY
I
RECOVERY
Back to top
- - - .
Page 39 of 82

QUINAF'RIL HYDROCHUIRIDE USP
7.6 ACCURACY:
The accuracy for each solvent were carried out by spiking different concentration
levels i.e. 80% to 120% of the internal limit to Quinapril Hydrochloride Batch
Number AH /05061108 and determining the actual concentration added (recovery).
Each level was injected 6 times.
Acceptance Criteria for Recovery: - 80% - 120% of the concentration of each

solvent.
7.6.1.1 Blank: N,N dimethyl formamide was used as blank

7.6.1.2 Diluent: N,N dimethyl formamide
7.6.1.3 Standard solution preparation was done as follows
n-Pentane 1.020
Acetone 1.070
IPA 0.20 0.203
4.
I
ACN
I
0.08
I
= 100 ml 2 ml Solution (A)
3 100ml
1 5.
- -
I DlPE
-
I 0.15 1 0.160 1'
6. Ethyl a&& 1.00 1.050
7. Toluene 0.18 0.182
- - - - -
Page 40 of 82

. -

QrmVAPRIL HYDROCHLORIDE USP
7.6.2. ACCURACY SOLUTIONS PREPARATION:
TABLE - 7.6.2-1 - STOCK SOLUTION FOR ACCURACY
TABLE - 7.6.2- 2 - PREPARTION OF ACCURACY SOLUTIONS

Volume of
Final volume Sample wt. Final Volume
Linearity levels Acc-A solution
with DMF in gm in vial
in ml
Level-1 (80%) 1.6 ml 100 ml 0.20 5ml
Level-2 (I 00%) 2.0 ml 100 ml 0.20 5ml
Level-3 (1 20%) 2.4 ml 100 ml 0.20 5ml
Page 41 of 82

RESlDUAL SOLVENTS - ANALYTICAL METHOD VALIDATION 1
7.6.3 RESULTS FOR STANDARD SOLUTION FOR ACCURACY:

Standard areas for accuracy obtained are as follows;
TABLE - 7.6.3 -1
Blank graph no.: 55
NMT 1 5 -0%
7.6.4 RESULTS OBTAINED FROM SAMPLE PRECISION:

TABLE - 7.6.4 - I
4 0.2018 ND ND ND ND ND MI ND 66
5 0.2017 ND ND ND ND ND ND ND 67
6 0.2014 ND ND ND ND ND ND ND 68 I
7.6.5 RESULTS OBTAINED FROM ACCURACY:

Accuracy levels are injected and the areas as obtained are as follows;
Page 42 of 82

7.6.5.a) For 80% level

TABLE - 7.6.5.a - 1
Blank Chromatogram No.:69
TABLE - 7.6.5.a- 2
TABLE - 7.6.5.a- 3
Page 43 of 82

QZlJNAPRIL HYDROCHLORIDE USP
7.6.5.b) For 100% level

TABLE - 7.6.5.b - 1
TABLE - 7.6.5.b- 2
TABLE - 7.6.5.b- 3
Acceptance
Criteria NMT 1 5 .O%
Page 44 of 82

RESXDUAL SOLVENTS - ANALYTICAL METHOD VALIDATION
1 QWAPRIL HYDR-RIDE USP
7.6.5.c) For 120% level
TABLE - 7.6.5.b- 2
TABLE - 7.6.5.b- 3
Page 45 of 82

7.6.6 SUMMARY ACCURACY:
Mean % recovery for each solvent is given as follows;
TABLE - 7.6.6-1
7.6.7 INFERENCE:
The % recovery was found to be within the limits from 91.08% to 103.77%.
7.6.8 CONCLUSION: Meets the acceptance criteria for accuracy
Page 46 of 82

r

b
Back to top
Page 47 of 82

Sample Information
Analysis Date & Time : 8/16/20056:24:33-PM
Llser Name : Admin
sample Name : QUTNAPRIL
Sample ID : BLANK
Data Name :E:\GC- L 7 A\GC-Data\QN-VALIDATIOMQN-VALID\
16080S\QN-11.gcd
Intensity - -
2000000 - - -
., ,.
-. :.
---
___ _
> ,
. . . . - - -
0 .. .. -- - -. . ... , - -
--
7-1- . .. , - - . . .
0 10 20
min

PARAMETER : ACCURACY
BIN NUMBER : 55 INST-NO. :AWADWOS
CHROMATOGRAM NAME :
DONE BY:

Sample information
User Name : Adrnin
Sample ID : 10Ph STD 1
Data Name : E:\GC-17 A\GC-Data\QN VALIDATION\QN-VALID\160805\QN-12.gcd
Method Name : E:\GC-I7 A\GC-METHO~S\QUMAPRILISK.gcm
instrument no : AH/ADL/o5
Intensity
2000000 - -- -

- --
695292
- -
-- 20 179783

PARAMETER :ACCURACY
BIN NUMBER : 5 /: INST.NO. :AWADLSOS a
DONE BY:
DATE: U\U\O<

Sample Information
User Name : Admin
Sample ID : 1000/0STD 2
Data Name : E:\GC- 17 A\GC-Data\QN-VALLDATIOMQN-VALTD\160805\QN-13
.gcd
Method Name :E:\GC-17 A\GC-MEmODS\QUWAPRn.gcm
Instrument no : AWADUOJ
L ~e&Tt.T&e,
L
2
11y5
-
1 .. .
Total
I
- - -
~
10.494 IPA--
, 12.917 DIPE
N m -
8.875 1 N-PENTANE
10.195 ACETONE-
1 14.189 ET-ACETATE
19.732 TOLUENE
-.
7-
-
Area
13347395 -.. -1
976953
80994
17---2$770
557929
729597 -
168908
15891546
,
1-
-
&~o/oP~
83.9905
6.1476
--.
..
0.5097
ALW3-
3.5109
--
4.591 1
1.0629
--
100.0000
A-
-
- , min
PRODUCT NAME : QUMAPRlL HCL RESIDUAL SOLVENTSVALlDATION

PARAMETER :ACCURACY
BMNUMBER: S+ 1NST.NO. : AHIADLIOS
DONE BY:
DATE :

Sample lnforrnation
User Name : Admin
Sample ID : 1000h STD 3
Data Name :E:\GC-17 A\GC-Data\QN~VAtIDATIOMQNNVALID\160805\QN~14.gcd
Method Name : E:\GC- I7 A\GC-METHODS\QUINAPRILl SK.gcm
Instrument no : AH/ADUOS
Intensity
2000000-r - - - - -- - - - - - I
7
I
1
l5000001
I I I
1 I
1000000-~
F
U
-I
500000 1
i YI
0
-
10
-- , - I - -- --7.-
T
20
--r --
min
-- - Peak Table - C@el l pr --
r ~ e a k # , Ret.Time , K
ame L e a Ar&+ - A
.pFIt 8.894 N-PENTANE L - 1 3 6 m --84.9921

2 10.221 ACETONE
3 10.525 IPA
4 10.919 ACN --
eq t---.
5
-.
t2.961 DIPE
14.225 ETHYL ACETATE
\ 19.755 TOLUENE
- --
&if@$&,.-
132272 -
3.4307
0.8264

PARAMETER :ACCURACY
BIN NUMBER: s& INST.NO. :AWADUOS
DATE : ~4\%\& DATE:

Sample information
User Name : Admin
S ~ mrn- l-eName
- ------ : OUINAPRIL
S;iple ID : COO%STD 4
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATION\QN-VLID\160805\QN_
15.gcd
Method Name : E:\GC- 17 A\GC-METHODS\QU!NAPRIL I SK.gcm
zb
min
Peak Table - Channel 1 -
Name Area . Area%

-
8.952 N-PENTANE 16092962 84.8948
10.284 ACETONE -.-1105260 1 5.8305
10.584 . I P A .- 92897 -- 0.4901
-.. - -
I 4 10.982 ACN 33232 0.1753

5 13.013 DIPE 662839 3.4967
-- 6 14.281 ETHYL ACETATE 802946 4.2358
7 19.799
_-- TOLUENE 166222-- I 0.8769
~ o t a l ~--- 18956358 _ 1 100.0000
PRODUCT NAPIE :QUiNAPRiL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :ACCURACY
BIN NUMBER : g q INST.NO. :AWADWOS
DONE BY: CHECKED BY :

Sample Information
User Name : Admin
Sample Name : OUINAPRIL
Sample ID : fjV0 s-jT
Data Name : E:\GC-17 A\GC-Data\QN VALIDATIOMON VALID\l60805\ON -
- - 16.gcd
Method Name : E:\GC- 17 A\GC-METHODS\QUINAPR(LI - S K ~ C ~
PRODUCT NAME :QUMAPRIL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :ACCURACY
B M NUMBER : 60 INST.NO. :AWADW05
DONE BY:
DATE :

Sample Information
User Name : Admin
Data Name : E:\GC-17 A\GC-Data\QN VALIDATION\QN VALID\160805\QN-17.gcd
Method Name : E:\GC-I7 A\GC-METHO~S\QUINAPRIL.~C~
Instrument no : AWADL/O5
- - .-- -- -
Peak Table Channel_I - --
1 Peak# Ret2Time Name are^_ Area%-
8.993 N-PENT- 13068337 - 83.7248
1 1
10.322 ACETONE 948463 6.0765
1 2
-- 3 10.620 IPA 103060 0.6603
4- 11.026 ACN - 34755 0.2227
5 13.054 DIPE 551471 3.533 1
6 14.324 .ETHYL ACETATE 757474 4.8529
7
rod
19.849 TOLUENE , 145117 -- 0.9297 ,
- 15@&77 -100.0000
, 1
PRODUCT NAME :QUMAPML HCL RESIDUAL SOLVENTS VALIDATION

BIN NUMBER : < 1NST.NO. :AHIADUOS
DONE BY:

QUINAF'RU, HYDROCHLORIDE USP
7.2.2 RESULTS:

TABLE - 7.2.2 -1
5 8.954 10.276 10.575 10.972 12.983 14.249 19.770 16

6 8.993 10.322 10.620 1 1.026 13.054 J 4.324 19.849 17
Average 8.924 10.248 10.546 10.943 12.97 1 14.238 19.770
SD 0.049 0.054 0.055 0.060 0.059 0.059 0.048
%RSD 0.55 0.52 , 0.52 0.55 0.46 0.42 0.24
Ppmce
Icriteria NMT 2.0%
TABLE - 7.2.2 - 2
6 13068337 1098208 103060 34755 551471 757474 145117 17

Average 15057619 1 170601 93718 35060 620943 793610 161993
SD 1926649.761 136445.8 19 1 1325.065 3872.080 74619.298 968 11.972 18716.029
NMT 15.0%
Page 14 of 82

MRTi HEALTHCARE LTD.
S ~ Qi ~I t % % mO F nann #wwsraresi rwmo
Sample Information
User Name : Admin
Sample ID : BLANK
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATIOMQNNVALID\I
60805\QN-I 8.gcd
Method Name : E:\GC-17 A\GC-METHODS\QUTNAPRIL.gcm
Intensity
2000000- - -
10 20
min
PRODUCT NAME : QUlNAPRlL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :ACCURACY
BIN NUMBER : dq ZNST.NO. :AWADWOS
CHROMATOCRAM NAME :
DONE BY:
DATE: nslaloc DATE :

Sample Information
(ICID3YsisDate & Time : 8/17/2005 12:44:08 AM
Cber Name : Admin
SrlJe Name
S g p l e ID
. .
- --
: SAMPLE I
- -- --
LYPNamc : E:\GC-I 7 A\GC-DataiQNNVALIDATIOMQNNVALID\

160805\QN- I9.gcd
b k h d Name :E:\GC-I7 A\GC-METHODS\QUINAPRIL.gcrn
Intensity
2500006 - -
20
min
1 PRODUCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

I
BIN NUMBER : 63 . 1NST.NO. :AWADWDS
CHROMATOCRAM N A M E :
DONE BY: &
DATE : 24\%!0< DATE :

AAFtTl HEALTHCARE LTD.
&W WSWN OI: MRI1 ICIDUSTREB i ilKITED
Sample Infomation
Analysis Date & Time : 8/17/2005 1:20:07 A M
User Name : Admin
Sam~leName : OUINAPRIL
Sample ID
Data Name
Method Name
lnshvment no
Intensity
2000000 - --- ---- -- - --- - - -- - --- -- --
1 PRODUCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION 1

I PARAMETER :ACCUIUCY
I
BIN NUMBER : 64 INST.NO. :AH~ADWOS
CHROMATOCRAM NAME :
DONE BY: _
& - CHEC
DATE : U\&\O<

n% rursrun 06 m n swo?isrrti~s
-!w~E?IYF.~
Sample information
Analysis Date & Time :8/17/2005 1:57:01 AM
User Name : Admin
~&~le~&ne : QUINAPRIL
Data Name : E:\GC-17 A\GC-Data\QN VALIDATIOMQN-VALID\ 16080S\QN-2 1 .gcd
Intensity
2000000-
-
'- ' ,-
0 - L
I._-_ - - -
----
-7 -- --
-7-f -
0 10 20
min

PARAMETER :ACCURACY
BIN NUMBER : 425- 4NST.NO. :AHIADWDS
CHROMATOGRAM NAME :
DONE BY:
DATE :

Sample Information
Analysis Date & Time : 8/17/2005 2:34:00AM
User Name : Admin
Data Name
Method Name
Instrument no
Intensity
2000000
I ' ..
0-
- --- - - -7
- --r
. : . . - __ . . ~-
-
,
- - .--- -~-. -
7--~
.~- -..- -\
--
.
0 10 20
min
-
PRODUCT NAME : QUINAPRL HCL RESIDUAL SOLVENTS VALIDATION

BIN NUMBER : 66 INST.NO. :AWADWOS -
CHROMATOGRAM YAME :
DATE: gU\(l\~<

Sample Information
Analysis Date & Time 3:10:49 AM
: 8/17/2005
User Name : Admin
Data Name : E:\GC- I 7 A\GC-Data\QN-VALIDATIOMQNMVALID\
160805\QN-23.gcd
Instrument no :AHIADLIOS
Intensity
2~00000 - - -- - . --
7-
7
- --- --
10 20
min

BIN NUMBER : 6 1NST.NO. :AHIADLIOS
CHROMATOCRAM NAME :
DONEBY: &
DATE : 2-416/o< DATE:

#%PiGrVtYrOH OF uR*i t W D U S ~ E 9L b M W
Sample Information
+Jndnd&ate & Time :811712005 3:48:09 AM
:Admin
F
le~&ne :QUINAPRIL
pie ID - :S M P L E 6
: E:\GC- 17 A\GC-Data\QN-VALIDATION\QN-VALID\
160805\QN-24.gcd
ata Name
ethod Name : E:\GC-17 A\GC-METHODS\QUMAPRIL.gcm
Instrument no : MIADUOS
Intensity -- -
- . - -- - ---- -
2000000 r -
A -- -
~'
1500000 -
500000-
'., -.
0 pp - , - 7 - -, ' - ' ' , - _ -- _ _ - -.
- , -
0 10 20
min
Peak Table Channel 1-

BIN NUMBER : 6% LVST.NO. :AWADMS
CHROMATOGRAM NAME :
DONE BY: d CHECKED BY :
DATE: ~q\gb< DATE :

AARTl HEBLTHCARE LTO.
nw owiSm*i OF a r l l P l IUWS*RiES *Ihglrn?S
Sample Information
Analysis Date & Time : 811712005 4:3 1 :05 AM
User Name :Admin
Sample ID : BLANK
Data Name : E:\GC-17 A\GC-Data\QN V A L ~ D A T I O N \ Q N - V A L ~ D \ ~ ~ O X ~ ~ \ Q N - ~ ~ . ~ C ~
Method Name : E:\GC-17 A\GC-METHODS\QUINAPRIL.~C~
Instrument no : AHIADYOS
Intensity
2000000- - -- ---. - - - - - -- - - -- - -
I
20
rnin

BIN NUMBER : gq INST.NO. :AWADWOS
CHROMATOGRAM NAME :
DATE :

Sample Information
User Name : Admin
Sample ID : 80% SPIKE 1
Data Name : E:\GC-17 A\GC-Data\QN-VALIDATIOMQNNVALID\160805\QN-26.gcd
Method Name : E:\GC-17 A\GC-METHODS\QU~ApRIL,gcm
Instrument no :AH/ADLIOS
20
min

PARAMETER :ACCURACY
BIN NUMBER: 3-0 INST.NO. : AWADUOS
CHROMATOGRAM NAME.
DONEBY: & ' CHECKED BY:
DATE : aqlgld<

Sample Information
Analysis Date & Time : 8/17/2005 5:52: 15 AM
User Name : Admin
Data Name : E:\GC- 17 A\GC-Data\QN V A L I D A T I O M Q N ~ V A L I D \ ~ ~ ~ ~ ~ ~ \ Q N ~ ~ ~ . ~ C ~
Method Name : E:\GC- 17 A\GC-METHODS\QUINAPRIL.~C~
Instrument no : AHJADWOS
20
min

PARAMETER :ACCURACY
BIN NUMBER : ?\ INST.NO. :AHIADWOS

DATE :

Sample Information
User Name : Admin
Data Name : E:\GC- I7 A\GC-D~~~\QN-VALIDATION\QN-VAL~D\~~O~O~\QN-~~.~C~
Method Name :E:\GC- 17 A\GC-METHODS\QURJAPRIL.gcm
min
-
Peak# Ret.Tie Name Area Area% --
1 8.8 16 N-PENTANE 10955008 84.7598
2 10.140 ACETONE 755730 - 5.8471
3 10.449 IPA - 77764 0.6017
4 10.833 ACN .. 25684 0.1987
5
7
6
Total
12.867
14.134
19.682
DIPE
ETHYL ACETATE 552210
TOLUENE
420143
138231
-
.- 12924770
3.2507
4.2725
1.0695
100.0000
4
PRODUCT. NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :ACCURACY
BIN NUMBER : 72 INST.NO. :AWADUOS

DATE: 24\81a4 DATE :

AARTl HEALTHCARE LFD.
isPl WirlSiO)r OP BARPt IHDUIiYRIES IWtPF9
Sample Information
Analysis Date & Time : 8/17/2005 7: 13:5 1 AM
User Name : Admin
Data Name : E:\GC- I7 A\GC-Data\QN-VALIDATmQN-VALID\ 160805\QN-29.gcd
Method Name : E:\GC-I7 A\GC-METHODS\QUINAPRIL.gcm
Instrument no :AWADWO5
Intensity
2000000~ - -
-- Area.-,--
1- Channel 1
-Peak Table - - -
-
PX
-
_
I
Peak# ~ e t . ~ i m L Nm--
2
I
.-3 - 10.544 A
-.4--- , 10.924 ACN
N-PENTANE
= - -
+
I 13771490-
10.241 ,ACETONE L - A 9 6 6 2 0 - -
-
, - 31320
80838
--
Area%- 4-
@.333--1
--5.5558--
-3..5009 -
ma
- J - --
5 1 12,962 ,DIPE - 1 547252 -

A 3310 - -,
-. 6
- , 14.225 !ETHYL ACETATL A U - -c 4.2217-.
-
, -
.-7 1 1 9 . 7 0 1 T Q L U L N E -4- 129669

-
0.8035
- - .---I
Total ; -- -.- , 16138502 I@.OOOL-
PRODUCT NAME :QUlNAPBlL HCL RESIDUAL SOLVENTS VALIUA'TION

PARAMETER :ACCURACY
BIN NUMBER : T3 1NST.NO. :AHIADWOS
CHROMATOGRAM YAME :
DATE :

Sample Information
User Name : Admin
Sample Name : QUINAPW
Sample ID : 80??SPIKE 5
Data Name :E:\GC-17 A\GC-D~~~\QN-VAL~DATION\QN~V~ID\~~O~O~\QN-~~.~C~
Method Name :E:\GC- I7 A\GC-METHODS\QUMAPRIL.gcm
Intensity - -- -
2000000 -- - - -- -
1
1
I
i m
'500000 l I
1000000
F
500000
0- T
r
- r---- - ----
l--T
0 10 20
min
-- Peak Table - Channel 1-

7- - -
p e a &Ret.Time . Name
-
A r e a _ _ _ Area% --
1 8.788 N-PENTANE - 9923026 84.3523 -
2 10.117 ACETONE 6895 I6 5.8613
3 10.423 IPA 63 124 0.5366
4 10.802 ACN 270 11 0.2296
5 12.827 DIPE 401506 3.4131
6 14.099 ETHYL ACETATE 519177 4.4134
I 7 -19,643 TOLUENE 140422 1.1937
I Total -. I 11763782 100.0000
PRODUCT NAME : QUlNAPRIL ACL RESIDUAL SOLVENTS VALIDATION

PARAMETER :ACCURACY
BM NUMBER : T4 INST.NO. :AWADWOS

DATE: d4\%10f DATE :

Sample Infonnation
Analvsis Date & Time : 8/17/2005 8:35:27 AM
userkame : Admin
Sample ID :80% SPIKE 6
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATION\QNYALID\160805\QN-3
1.gcd
Instrument no :AHIADUOS
-- -- - Channel 1 --
Peak Table
:f#p%x lI 83.9698
pp
N m e - A
8.791 !N-PENTANE 10362412 - -1 - I
745275
0.2536 -1
564035
1.1980

PARAMETER :ACCURACY
BIN NUMBER : 7s INST.NO. :AWADWOS
DONE BY:
DATE: 24\6!o< DATE :

' Samole Information
Analysis Date & Time :8/17/20059:16:18AM
User Name : Admin
Sample ID : 1000?SPLKE 1
Data Name :E:\GC-i7 A\GC-Data\QN VALIDATION\QN-VAtID\I 60805iQN-32.gcd
Method Name : E:\GC- 17 A\GC-METHODS\QUINAPNL.~C~
- -
Ft;
I 0
500000-1
I I
I, , - --
I
I F " ' I " l ' l I "

0 10 20
min
Peak Table - Channel I ,

Peak# &t.~ime Name Area.
1 8.898 N-PENTANE 12867630
2 10.227 ACETONE 944907
3 10.539 IPA 83865 _
4 10.921 ACN 34627
537557
- --
PRODUtT NAME :QUWAPRIL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :ACCURACY
BtN NUMBER : -7 INST-NO. :AWADUOS
CHROMATOGRAM NAME . 100 ' /-
DONEBY:
DATE : 24 (%(o< DATE:

Sample Information
User Name :Admin
Sample Name :QUINAPlUL
Sample ID : 1Wh SPIKE 2
Data Name : E:\GC- I7 A\GC-Data\QN-VALIDATIOMQN-VALID\
160805\QN-33.gcd
Method Name : E:\GC- 17 A\GC-METHODS\QUMAPRIL.gcm
G
LL-+
/
- A -
IT-
0 10 20
min
Peak Table - Channel 1 - -- -
8.898 N-PENTANE
2 10.227 ACETONE
3 10.539 IPA _ _
, 4 . 10.921 ACN
4.5853
Total

BIN NUMBER : T+ 1NST.NO. : ARIADM5
DONE BY:
DATE : w 18 lo< DATE :

Sample information
User Name :Admin
Sample ID : I OOQhSPIKE 3
Data Name : E:\GC- 17 A\GC-Data\QN VALIDATIOMQN VALID\ 160805\QN-34.gcd

Peak# Ret.Time Name -- Area Areayo
1 8.927 N-PENTANE 13435050 . 83.9771
2 10.263 ACETONE 943380 - 5.8967
3 10.568 PA 100801 0.6301
4 10.960 ACN 363 82 0.2274
5 12.992 DWE 55 1233 3.4455
6 14.268 E T H n ACETATE 763378 4.7716
i 7 19.782 TOLUENE 168242 1.0516
1 Total 15998466 100.0000 -..
I PRODUCT NAME :QUMAPRIL HCL RESIDUAL SOLVENTS VALIDATION

I
B M NUMBER : 39 MST.NO. : AWADWOS

DATE : e ~ \105-
e

AAKII HEALWARE LTD.
A N I>IVIb(DNOt. M R T f IUDhrSTZgRFP; LfMT"ETi
Sample Information
User Name : Admin
Sample Name :QUINAPW
Data Name : E:\GC-17 A\GC-Data\QN-VALIDATION\QN-VfiID\I
60805\QN-35.gcd
Method Name :E:\GC-17 A\GC-METHODS\QUMAPRIL.gcm
min

-
--
Peak# I Ret.Time
- -
Name- r K - p 4
-
--
- Are@%~
-
-I :
L I p 4 q N - P E N T A IB J 15 ~ 1069 19 - -- 84.7635
2 10.290 ACETTONE- 976501 5.4791 - -
Total i _ .
, .- -P - -- --
I PRODUCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

I
PARAMETER :ACCURACY
BIN NUMBER : 7 KNST.NO. :AHIADWOS
CHROMATOGRAM YAME :
DATE: Z U \ S ~ DATE :

Sample Information
Anaiysis Date & Time : 8/17/200511:59:33 AM
User Name : Admin
Data Name :E:\GC- 17 A\GC-Data\QN-VALIDAmQN-VALID\l 60805\QN036.gcd
Method Name : E:\GC- 17 A\GC-MEmODS\QUMAPRIL.gm
Instrument no : AWADLJOJ
Intensity -
20000007 --
1500000
w
I
1 'I
F
u
u
50000
i
0
0 10 20
min
-
t
-
Area% 7
5.8928 -
4.3435
I

PARAMETER :ACCURACY
BIN NUMBER : 40 lNST.NO. :AWADMS
DATE :

Sample Information
User Name : Admin
Data Name : E:\GC-17 A\GC-Data\QN VALIDATIOMQNYALID\I 60805\QN-37.gcd
Method Name : E:\GC-I7 A\Gc-METHo~S\QUINAPRIL.~C~
P R O D U O NAME : QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :ACCURACY
BIN NUMBER : 81 INST.NO. :AWADWOS
CHROMATOGRAM NAME
N E B & :
DATE: QLI ) 8 ! ~ DATE:

AARR HEALTHCARE LTQ.
API LWIISIOW OF AARYt INDGSTR!ES LIMi-D
Sample Information
User Name : Admin
Data Name : E:\GC-17 A\GC-Data\QN-VAL1DATIOMQNNVALln\160805\QN-38.gcd
Intensity
2000000-
-
.
-
-
Peak#
i
7
~
7--
ee . -
8.93LN-PENT_AB
x 2 7 4 A-CETaNE-
Peak
-
t _N=
-
-7
-1
- Table Channel 1
Area -. -
2019837L
-
-
1233584
- -
Area%
85.207 -1
5.2039 --
-.
-
,
3 _ K ! 3 3 2 t ~ ~ --
- 4-&93j--ACN-- -
-
-!
127120
4 6 5 4 8 -
- -- 0.5363
0,1964
3.4155--,
-
L T O L -

PARAMETER :ACCURACY
BIN NUMBER : Rx INST.NO. :AWADWDS
CHROMATOGRAM YAME :
DONE BY:
DATE :
&
941.g10 <
' q Q 1
r
DATE :
' E ~ ~
7/c
~ ~

A A M I HEALTHCARE LTD.
R W MVIW ae nrvPrz awCt&s'w!%s.~hsr-~n
Sample Information
Analysis Date & Time I 8/17/2005 2:01:54 PM
User Name ~dmin
Sample Name :OUINAPRIL
Sample ID : (20% SPIKE 2
Method Name : E:\GC-17 A\GC-METHO~S\QUINAPRIL.~C~
Intensity
2000000-- -
20
min
-.- -- - - Peak Table - Channel 1- - .-- -
N a m e -I-
--
e t ,--
~ e a k n ~.~ime.
I _ . 8.964 _N-PENTANE_ I
2110.31LACETONEEp -1.
-- Arec
-
21225792
1282321
,- -_ Area% .-
,-- 8 5 . 6 2 6 4
5.1730 _
4
, 3
4 .
]0.620 , IPA
11.005 IACL---
5 _ 13.047 DE-p-L.-
-. lm2-
- 47884
815846 -;
. -0=49701--.
.- 0.1932 --
3 m 4
--
6 , 14.313-_mHYLACETATEi 1091120 ' 4.4011--- 1

7 , 19.825 1TOLUENE 202653 - , .. 0.8175- - -
Tots,, ! =
-
:
1
48
2
8 -- 100.0000
- -
I PRODUCT NAME :QUAAPIIL HCL RESIDUAL SOLVENTS VALIDATION

I
PARAMETER :ACCURACY
BIN NUMBER : rr)rST.No. :AWADWO5
CHROMATOGRAM NAME :
DATE : DATE :

R P ~WASION W )CTl1&.1BL1STRIES LIWITED
Sample Information
Analysis Date & Time : 8/17/2005 2:42:45P M
User Name : Admin
Sample Name : QUiNAPRIL
Data Name : E:\GC-17 A\GC-Data\QN-V~1DATIOMQN~VA1,1D\160805\QNN40.gcd
Method Name : E:\GC- I 7 A\GC-METHODS\QUINAPRIL.gcm
Instrument no :AHIADWOS
Intensity
2000000-, .-- - --
Peak#
-:
1
-
-
5
6-
--
7 -
Total ,
.
- - -
I 13.052 D P E
=ETHYL
19.822
-
-
-
Ret.Time - Name . .
8.97a~-PENTANE-
k3 T m 2 4 + - -1 ACETONK
4
- 10.618 ,IPA
jt 11.003 A m --
-
-
-
7--
.-
117w.--
ACETDATEImg2 -
.TaUENE- .
-
5
.
h. -
19550643
+-
-
----
1152958 --
4- - L 2 6 m
-
22867469 - _
A
-
.
-
- -
--
-
-
- -
-
-
-
Area%
85.4954
5.041P
0.5512--
0.2139
3dBo
44264-
0.9431-
100.000~
'
-
-
-
-
-
-
-
PRODUCT NAME : QUlNAPRlL HCL RESlDUAL SOLVENTS VALIDATION

PARAMETER :ACCURACY
BlN NUMBER : a4 INST.NO. :AH/ADL/OS
CHROMATOGRAM YAME -
DONE BY:
DATE : DATE :

Sample Information
Analysis Date &Time 3:23:34 PM
: 8/17/2005
User Name : Admin
Sample Name :QUMAPW
Data Name :E:\GC-17 A\GC-Data\QN-VALIDATION\QN-VKID\l60805\QN-41
.gcd
Method Name gcm
: E:\GC- 17 A\GC-METHODS\QUmAPRIL.
Instrument no :AWADUOS
Intensity --- -- - - - - --- 7- -
2000000
1A i
1500000 j
1
0000001
i
500000
es
1 -- --. - -
-
2
->-"'- 1
* . I
~%--
o m = - - - I - - - 7-7- 7------- 1
0 10 20
min
-- -- I - -
-
Peak Table Channel 1-
-
.
Peak# Ret.Time Name Area -

area_"/^ -
1 8.862 N-PENTANE 16074171 84.3440
2 10.209 ACETONE 1169175 6.1349
. 3 10.516 TPA 111153 0.5832
4 10.894 ACN 42252 0.2217
5 12.936 DXPE 620674 3.2568
6 14.220 ETHYL ACETATE 836875 4.3912
7 19.760 TOLUENE 203584 . 1.0682
- Total 19057884 100.0000
PRODUCf' NAME :QUINAPRIL HCL RESlDUAL SOLVENTS VALlDATlON

PARAMETER :ACCURACY
BINNUMBER: G 5 INST-NO. :AHIADUOS
CHROMATOGRAM NAME :
DATE: ga\%(a< DATE :

Sample Information
Analysis Date & Time : 8/ 17/2005 4:04:25 PM
User Name : Admin
sample ID : f20% SPIKE 5
Data Name : E:\GC-17 A\GC-Data\QN-VALIDATION\QN-VALID\
I60805\QN-42.gd
Method Name : E:\GC- I7 A\GC-METHODS\QUINAPRIL.gcm
Instrument no :AWADWOS
Intensity
I
--
2000000 - -
2
2-
1500000 4
0
~
1000000
E
!i
500000
I
1 \---I
O- I-. , , , , , , T - 7 - 7 - 7 s I I 8
-___
1 1
__
8 - 7
+
7
/
7 -
2b
7 - - 4
min

PARAMETER :ACCURACY
BIN NUMBER : S6 INST.NO. :AWADWOS
DATE : Q4\ 8 \0< DATE :

Sample Information
User Name : Admin
Data Name : E:\GC- I7 A\GC-Data\QN-VALIDATIOMQN-VALID\
160805\QN-43.gcd
Instrument no : AH/ADW05
.-- Peak Table - Channel 1

Peak# Ret.Time _ Name Area Area%
1 8.84 1 N-PENTANE 15350126 , 84.2323
2 10.177 ACETONE 1159220 6.3611
3 10.487 IPA 102160 0.5606
4 10.860 ACN 34932 0.1917
5 _ 12.898 DIPE 622831 3 3.4177
6 14.171 ETHYLACETATE- - 791251 1 4.3419
7 19.700 TOLUENE 1630461-A- 0.8947
Tehl 18223566 ; _ 200.0000

PARAMETER :ACCURACY
BIN NUMBER : INST.NO. :AH/ADL/OS
DONE BY:
DATE : DATE :

RESIDUAL SOLVENTS - ANALYTICAL METHOD VALIDATMlN
QULNAPRIL HYDROCHLORIDE USP
7.7 RUGGEDNESS /
INTERMEDIATE PRECISION
Back to top
Page 48 of 82

I

7.7 RUGGEDNESS / INTERMEDIATE PRECISION:
Ruggedness was carried out by checking the system suitability by a different

analyst and instrument on a different day and comparing the results, as vrell as
analyzing ths same sample six times.
7.7.1.1 Blank: N,N dimethyl fomamide was used as blank.

7.7.1.2 Diluent: N,N dimethyl formamide.
7.7.1.3 System suitability solutions:
manner:
TABLE - 7.7.1.3-1
Page 49 of 82

7.7.2 RESULTS:

TABLE - 7.73-1
Average 6.942 7.937 8.237 8.482 10.291 1 1.278 15.796

SD 0.0 12 0.010 0,010 0,010 0.009 0.010 0.009 -
YoRSD 0.18 0.12 0.12 0.12 0.09 0.08 0.06
Acceptance
NMT 2.0%
criteria
TABLE - 7.7.2-2
NMT 15.0%
- - - - - - - - - - - -
Page 50 of 82

7.7.3 INFERENCE:

1. The ?4RSD of retention time was 0.06 to 0.19.
7.7.4 CONCLUSION: Meets the acceptance criteria for system precision.

7.7.5 CHROMATOGRAMS: Chromatograms are given on the following pages along
with calculation sheet.
TABLE - 7.2.5 - 1

ppp

-. - -. - - - - -
Page 5 1 of 82

Page 1 of 1
Software Version : 6.2.1.0.104:0104 Date : 8/23/20051:34:43 PM

Sample N a m e : BLANK Data Acquisition Time : 8/22/20051: 12:16 PM
Instrument Name : GCHS Channel :A
Tiack/Vial : OjO Operator : manager
Sample Amount : 1.000000 Dilution Factor : 1,000000
Cycle : 1
Result File : D:\GC-DATA\QUINAPRIL-DATA\220805\qn-00

1 .rst
Sequence File : D:\GC-SEQUENCE\QN220805. seq
l l l l l l i l lil l l l l ] l l l l ] i ~ l l ~ ~ ~ ~ ~ 1 ~ ~ ~ ~ ~ 1 ~ ~ 7 7 T
2 4 6 6 10 12 14 16 18 20 22 24
Time [ m d
AARTl HEALTH CARE LTD
No peaks available to report

PARAMETER NAME : CHRO. NO. :
DONE BY CHECKED BY :

Page 1 of 1
Softwareversion : 6.2.1.0.104:0104 Date : 8/23/20051:34:55 PM
Sample Name : BLANK Data Acquisition Time : 8/22/20051:54:20 PM
Instrument Name : GCHS Channel : A
Rack/Vial : 0/0 Operator : manager
Sample Amount : 1.000000 Dilution Factor : 1.000000
Cycle : 2
Result File : D: \GC-DATA\QUINAPRIL-DATA\220805\qn-002.rst

Sequence File : D: \GC-SEQUENCE\QN_220805,seq
~IrwnmmipwlwITIrirminw~ mwjmmmivTl-
2 4 6 8 10 12 14 96 18 20 22 24
Time [rnin]


Page 1 of 1
Software Version : 6.2.1.O.104:O104 Date : 8/23/20051:35:10 PM

Sample Name : STD 1 Data Acquisition Time : 8/22/20052:38:12 PM
Rack/Vial : 0/0 Operator : manager
Cycle : 3
Result File : D:\GC-DATA\QUINAPRIL-DATA\220805\qn-003.rst

Sequence File : D: \GC-SEQUENCE\QN-220805.seq
2 4 6 8 10 12 14 16 18 20 22 24
Time [rn~n]
Peak Component Time Area Area Height

# Name [min] [uV*sec] ["/.I luvl
1 n-PENTANE 6.955 5107489.93 86.05 988528.21
2 ACETONE 7.947 339420.27 5.72 75329.91
3 IPA 8.246 25958.00 0.44 4583.15
4 ACN 8.491 11596.76 0.20 2320.68
5 DIPE 10.301 194909.55 3.28 35207.64
6 ETHYL ACETATE 11.287 212407.13 3.58 47326.14
7 TOLUENE 15.805 43385.67 0.73 10183.59
5935167.30 100.00 l.l6e+06
Warning -- Signal level out-of-rangein peak
- - -
PARAMETER NAME : R U F F g CHRO. NO. :

DONE BY
&ba CHECKED BY : 5
5zs10B'-

Page 1 of 1
Software Version : 6.2.1.0.104:0104 Date : 8/23/20051:35:20PM

Rack/ Vial : O/O Operator : manager
Sample Amount : 1 .OOOOOO Dilution Factor : 1.000000
Cycle : 4
Result File : D:\GC-DATA\QUINAPRIL-DATA\220805\qnnO04.r&

Sequence File : D:\GC-SEQUENCE\QN-220805.seq
- Iv IL 0- nv mw 20 22 24
Time [m~n]

# Name [min] [uVtsec] [%I IuVI
1 n-PENTANE 6.949 4889869.98 85.53 988435.28
2 ACETONE 7.941 340423.13 5.95 75218.78
3 IPA 8.243 26442.21 0.46 4601.21
4 ACN 8.485 12717.91 0.22 2372.11
5 DIPE 10.295 192937.89 3.37 34885.18
6 ETHYL ACETATE 11.284 2121 10.59 3.71 47682.97
7 TOLUENE 15.803 42533.81 0.74 10105.36
5717035.52 100.00 1.16e+06
Warning -- Signal level out-of-range in peak

I
PARAMETER NAME : RU CHRO. NO. :

Page 1 of 1
Softwareversion : 6.2,1.0.104:0104 Date : 8/23/20051:35:26 PM

Rack/Vial : O/O Operator : manager
Cycle : 5

Time [rnln]
AARTI HEALTH CARE LTD

# Name [min] [uV*sec] [YO] [uvl
1 n-PENTANE 6.931 5153392.24 85.32 988661.26
2 ACETONE 7.932 365295.12 6.05 80330.74
3 IPA 8.233 28487.59 0.47 4940.24
4 ACN 8.476 13363.16 0.22 2509.96
5 DIfE 10.287 206496.64 3.42 37709.78
6 ETHYL ACETATE 1 1.274 226763.52 3.75 51755.43
7 TOLUENE 15.793 46499.84 0.77 11000.81
6040298.10 100.00 1.18e+06

I
PARAMETER NAME : RUG CHRO. NO. :
/

Page 1 of 1
Software Version : 6.2.1.0.104:0104 Date : 8/23/2005 1:35:36 PM

Sample Name : STD 4 Data Acquisition Time : 8/22/2005 4:52:57 PM
RackjVial : 010 Operator : manager
Sample Amount : 1.OOOOOO Dilution Factor : 1.000000
Cycle :6

Sequence File :D:\GC-SEQUENCE\QN-220805.8eq
8 SG
113
N
-'i
l--
N
0
F
i:
0 rT)
i
7
7-
1 "
1
1
1
+
I
2
I - -
4 6
r
%
$
a
8
B
w
" E
10
>
A
14
z
w
3
P
IL
I L~ /----
1 1 1 1 ~ l I I l / I I I ~ l ! I I I I ! l ~ ~ I l I I ~ i I I I ~ l l l l ~ l l l l ~ l l l 1 ~ l 1 l l ~ l l l l ~ l l ~ ~ l l l l ~ l l l l ~
12 16 18 20 22 24
I
T~me[ m d

# Name Iminl [uV*sec] IN1 [uVI
1 n-PENTANE
2 ACETONE
3 IPA
4 ACN
5 DIPE
6 ETHYL ACETATE
7 TOLUENE

I
PARAMETER NAME : RUG EDNESS CHRO. NO. :
DONE BY k M \ bcio5 CHECKED BY :

Page 1 of 1
Software Version : 6.2.1.0.104:O 104 Date : 8/23/2005 1:35:48 PM

Sample Name : STD 5 Data Acquisition Time : 8/22/2005 5:39:45 PM
Rack/Vial : O/O Operator : tcprocess
Cycle : 7


-
# Name [min] [uV+sec] ["/.I [uVI
1 n-PENTANE 6.931 5218542.32 85.90 988552.23
2 ACETONE 7.928 350454.04 5.77 76714.98
3 IPA 8.229 27184.75 0.45 4864.03
4 ACN 8.474 12940.63 0.21 2449.04
5 DIPE 10.283 201846.65 3.32 36448.61
6 ETHYL ACETATE 11.268 219281.95 3.61 49 104.93
7 TOLUENE 15.785 45177.66 0.74 10659.93
6075427.99 100.00 1.17e+06

I

Software Version : 6.2.1.O.104:O 104 Date
Page 1 of 1
: 8/23/20051:35:56 PM
I
Sample Name : STD 6 Data Acquisition Time : 8/22/20056:37:46PM
Rack/Vial : 0/0 Operator : tcprocess
Cycle : 8
Result File : D: \GC-DATA\QUINAPRILDATA\220805\qnn008.rst


# Name [min] [uV*sec] ["/.I [uVI
1 n-PENTANE 6.956 4488322.86 85.63 941472.52
2 ACETONE 7.948 312950.62 5.97 68821.78
3 IPA 8.248 24371.92 0.46 4367.92
4 ACN 8.494 11246.32 0.21 2180.41
5 DIPE 10.301 172250.31 3.29 31055.64
6 ETHYL ACETATE 11.288 192483.18 3.67 42928.17
7 TOLUENE 15.804 39777.79 0.76 9122.52
100.00 1.10e+06
PARAMETER NAME : CHRO. NO. : qCT

DONE BY CHECKEDBY :

QUINAF'RlL HYDROCHLORIDE USP
7.7.6 METHOD PRECISION :
For intermediate precision was determined by injecting six sample preparations

fromthe same batch - batch number - AH /0506/108 and quantitjling the solvents
present in the batch as well determining the % RSD of the retention time, area and
AW0506f 108, and estimating the content of residual solvents:
TABLE - 7.7.6 1 -
Page 52 of 82

RESIDUAL SOLVENTS - ANALYTICAL METWOD VAlLWATION
QUnVAPRIL HYDROCHLORIDE USP
7.7.7 RESULTS:

TABLE - 7.7.7 - 1
%RSD NA NA NA NA NA NA NA
Acceptance
NMT 2.0%
criteria
TABLE - 7.7.7 - 2
Acceptance
NMT 15.0%
criteria
Page 53 of 82

I
7.7.8 INFERENCE:
1. The area for n-Pentane, acetone, isopropyl alcohol (IPA), acetonitrile (ACN),
dj isopropyl ether (DIPE), ethyl acetate and toluene was not detected in sample.
2. The % RSD of content was not applicable.
7.7.9 CONCLUSION: Meets the acceptance criteria for method precision
3 39 Sample-2 (Method precision)

6 I 02 Sample5 (Method precision)
7 103 Sampled (Method precision)
7.7.11 COMPARISON:
Back to top
Page 54 of 82

Page 1 of 1
SoftwareVersion : 6.2.1.0.104:0104 Date : 8/23/2005 1:36:07 PM

Sample Name : BLANK Data Acquisition Time : 8/22/2005 7:19:50 PM
Rack/Vial : 010 Operator : tcprocess
Cycle : 9
Result File : D:\GC-DATA\QUINAPRIL-DATA\220805

\qr~O09.rst

PARAMETER NAME : CHRO. NO. : 96

Page 1 of 1
Softwareversion : 6.2.1.0.104:0104 Date : 8/23/2005 1:36:17PM

Sample Name : BLANK Data Acquisition Time : 8/22/2005 8:O150 PM
RacklVial : 010 Operator : tcprocess
SampleAmount : 1,000000 Dilution Factor : 1.000000
Cycle : 10
Result File : D: \GC-DATA\QUINAPRIL-DATA\220805

\qn-0 lO.rst
AARTl HEALTH CARE L I D

t
PARAMGTER NAME : R U G ~ , ~ ~ , 0 5 CHRO.NO. : 47

DONE BY

Page 1 of 1
Software Version : 6.2.1.O.104:O 104 Date : 8/23/20051:3626PM

Sample Name : TEST 1 Data Acquisition Time : 8/22/20058:43:51 PM
Cycle : I1

l.rst
Sequence File : D:\GC-SEQUENCE\QN_220805.%q
N o peaks available to report
PARAMETER NAME : CHRO.NO. : 9 8


Page 1 of 1
Software Version : 6.2.1.0.104:0104 Date : 8/23/20051:36:32 PM

Sample Name : TEST 2 Data Acquisition Time : 8/22/20059:25:52 PM
Rack/Vial : 0/0 Operator : tcprocess
Cycle : 12
Result File : D:\GC-DATA\QUINAPHLDATA\220805\qn-012.rst

Sequence File : D:\GC-SEQUENCE\QN_220805,seq
Time [min]

PARAMETER NAME : RUGG
DONE BY

SoftwareVersion : 6.2.1.0.104:0104 Date : 8/23/20051:36:40PM
Sample Name : TEST 3 Data Acquisition Time : 8/22/200510:07:53PM
Rack/Vial : O/O Operator : tcprocess
Cycle : 13

P I I ~ I I I I ~ I I I I ~ I I ~ ~ I I I ~ ~ ~ I ~ I I I I ~ ~ I I ~ I ~ I I ~ ~ I IR ~I I ~I I :I I~I II II I I T~ ]I TI ~ ~~ ~I ~ I I I I
2 4 6 8 10 12 14 I6 18 20 22 24
T~me[min]
PARAMETER NAME : RUGG DNESSgt0g CHRO.NO. :

DONE BY &?%.A\0 CHECKED BY :

Page 1 of 1
Software Version : 6.2.1.O. 104:0104 Date : 8/23/20051:36:49 PM

Sample Name : TEST4 Data Acquisition Time : 8/22/200510:49:54PM
Rack/ Vial : O/O Operator : tcprocess
Cycle : 14

14.rst
PARAMETER NAME : RUGG CHRO. NO. : lo \


Page 1 of 1
Softwareversion : 6.2.1.0.104:0104 Date : 8/23/2005 1:37:01 PM

Sample Name : TEST5 Data Acquisition Time : 8/22/2005 1 1:31:55 PM
Cycle : 15
Result File : D:\GC-DATA\QUINAPRIL-DATA\220805\qn-0 15.rst

Sequence File : D:\GC-SEQUENCE\QNJ20805.8eq
PARAMETER NAME :
DONE BY CHECKEDBY :

Page 1 of 1
Sof~areVersion : 6.2.1.0.104:0104 Date : 8/23/2005 1:37:09 PM

Sample Name : TEST6 Data Acquisition Time : 8/23/2005 12:13:56 AM
Cycle : 16

4
r?
I
+-
2 o q
_1
I -
3
g 2
2 , o q
I _ -
-2
0
i
I
I 2 4 6 8 I 10 12 14 16 ~ 18 20 22 24 ~
Thme [rn~nl
N o peaks available to report
PARAMETER NAME : RUGG CHRO.NO. : 4 0 3


1 QUINAPRIL HYDROCHLORIDE USP I
7.8 ROBUSTNESS
7.8.1 CHANGE IN FLOW RATE k 10%
7.8.1-a FLOW RATE -10%
SYSTEM PRECISION
Back to top
Page 55 of 82

7.8.1-a Flow rate change 1.53 mumin
Robustness was carried out by checking the system suitability by changing the
flow rate (* 10%) and comparing the results, as well as analyzing the same sample.
7.8.1-a.1 STANDARD SOLUTIONS PREPARATION:
7.8.1-a. 1.1 Blank: N,N dimethyl formamide was used as blank.

7.8.1-a.1.2 Diluent: N,N dimethyl formamide
7.8.1 -a.1.3 System suitability solutions:
manner:
-
TABLE 7.8.1-a.1.3 -1
n-Pentane 1.030
Acetone 1.150
0.20 0.212
3 100 m! 2 ml Soiution (A)
4. ACN 0.08 0.083 -
(solution A) 3 100rnl
5.
-. DIPE 0.15 0.164
6. Ethyl acetate 1 .OO 1.020
7. Toluene 0.18 0.178
Page 56 of 82

7.8.1-a.2 RESULTS:
Blank Chromatogram No,: 104

TABLE - 7.8.1-a.2 -1
Average 10.141 1 1.563 11.861 12.270 14.359 1 5.666 20.988

SD 0.092 0.086 0.078 0.083 0.083 0.075 0.015
%RSD 0.90 0.75 0.66 0.68 0.58 0.48 0.07
Acceptance
NMT 2.0%
criteria
TABLE - 7.8.1-a.2 -2
b
- -
Average 1 692628 907387 93956 31590 472398 642376 223232

SD 1574057.371 98372.324 12396.660 4304.833 63953.829 68375.726 26581.858
NMT 15.0%
Page 57 of 82

7.8.1-a.3 INFERENCE:
1. The % RSD of retention time was 0.07 to 0.90.
7.8.1-a.4 CONCLUSION: Meets the acceptance criteria for system precision.
7.8.1-a.5 CHROMATOGRAMS: Chromatograms are given on the following pages

along with calculation sheet.
- - - -- - -
Page 58 of 82

Sample Information
Analvsis Date & Time PM
: 8/20/20055:08:01
usehame : Admin
Sample ID : BLANK ( Flow = 1.53mll1nin)
Data Name : E:\GC-17 A\GC-Data\QN~VALIDATION\QN~VALID\200805\QN~OI.gcd
Method Name : E:\GC- 17 A\GC-METHODS\QUINAPRIL-LF.gcrn
Ins~rumentno : AHIADLIOS
Intensity
2000000 -
min
PHODLJCI' NAME :QtIlNAPRIL HCL RESIDllAL SOLVENTS VALIDATION

PARAMETER : ROBIJSTNESS
BIN NIIMBEK : i04 INST.NO. : AWADLIOS
CHROMATOGRAM NAME : ~lanlc A
DONE BY:
DATE :

AARTI HEALTHCARE LYD.
s w
AfJ1 i ~ ~ z U* ~ dh
z ~ s,mr,S=tlI 5 - I N-lq
Sample Information
Analysis Date & Time : 8/20120055:50:44 PM
~ser~arne : Admin
Sample Name QUINAPRIL
Sample ID : 100% STD ( Flow = 1.53mlimin)
Data Name : E:\GC- 17 A\GC-Data\QN VALIDATION\QN-VAL1 D\200805\QN-02.gcd
Method Name : E:\GC-17 A\GC-METHODS\QUINAPRIL-~~.gcm
Intensity .-.
2000000
min
- --
P g k Table - Channel 1
k t. T - k Name - Area - -
1 10490 _N-PENITAXE . 113_63!1- -
2 _ I 1.620 AcETQ_NE-- - 867199 - -
3- 11.914 [ P A - 93666
- - -
-
A
4
.. 12.328 ACN -. 2U3 - -
5 - 14.417 DIPE --- 450068 -- --
6 -
15.717 ETLYL G E T A T E - 618216 - -
7- ~~Tw~-ToLu!E -- 251869
- - -
Total -
13671992
PRODUCT NAME :QUlNAPRIL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER : ROBUSTNESS
BIN NUMBER : \o< 1NST.NO. :AH/ADWOS
CHROMATOGRAM NAME :
DONEBY: 6
DATE : w\&<

@M R T I HEAUHCARE LTD.
API UlblSWN UC A 6 9 1. + W L . % ~ R £ F R MITE 12
Sample Information
Analysis Date & Time PM
: 8/20/20056:33:05
User Name : Admin
Sample ID : 100% STD ( Flow = 1.53ml/min)
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATiON\QN-VALIDDO0805\QNO3
.gcd
Method Name : E:\GC-17 A\GC-METHODS\QUINAPRiL-LF.gcm
Intensity -._ - - - - - --. - --
2000000 --
W
- -
, z
2
I, Zi
! $
1500000- *
0
N
10 20
min

P&# ~ z 1 e Area
- - -
1 .- N - P E W A N L - 15-7
-
-2 ACEToNE - - 1103708
3 IPA 11248
4 A_CN 39776.
5 DIPE . 6N422 - -
6 ETHYL ACETATE . - 775050
7 TOLUENE 2713:
Total 17922674

BIN NUMBER : 1o6 INST.NO. :AWADWOS
DATE :

QMI HEALTHCARE LTD.
API T ; ' W I ~ D N (IF ~ i i ~ a C 2~T1 : * ~ i s zh+r**
Samole Information
Analysis Date & Time : 8/20/20057: 15:53 PM
user-Name : Admin
Sample ID : 100% STD ( Flow = 1.53ml/min)
Method Name : E;\GC- 17 A\GC-METHO~S\QUINAPRIL-LF%
Intensity
2000000 iL1
Z
i
I L
20
min

Ret.Time
--
Name _ - Area --Area%.
10.003 N-PENTANE -- 1ON82lL
- , 83.13 16
11.428 ACETONE .- - 838950- ; 6.477
4.743 _ A C E T O N E + 90028 -
_- 0.6898-
12.142 ACN _- - - 28321 .- X17_0
14.226 -
- 428784. --3.2854
6 1 5 x 4 ETHYL ACETATE
' 54a1 - - - 4.5529
7 20.978
-- _TOUENE - 221304 A ]A956 -
Total - - 13051379 , ~00.00~~
/ PRODUCT NAME :QUlNAIRIL HCL RESIDUAL SOLVENTS VALIDATION

I
PARAMETER : ROBIIS'TNESS
BIN NUMBER : (03 1NST.NO. : AHIADLIOS
Sm mi%3
DATE :

Sample Information
User Name : Admin
Sample ID : 100% STD ( Flow = 1.53mllmin)
Data Name : E:\GC- 17 A\GC-Data\QN VALIDATION\QN VALIDV00805\QN-05.gcd
Method Name : E:\GC- I7 A\GC-METHOBS\QUINAPRIL-LF&~
Intensity
2000000
20
min
P!&Table - Channel 1
6
7
Total

PARAMETER :ROBUSTNESS
BIN NUMBER : \0g 1NST.NO. : AWADWOS
CHROMATOGRAM NAME :
DONE BY:
DATE : 2.q\~\d

Aial i'LdlZtC1M CSI (idFtF2 'F.tl' ''PFd; 'WsyCL
Sample lnforrnation
Analysis Date & Time : 8120120058:41 :31 PM
1-Iser
- -.Name
. - ... : Admin
Sample Name . 7 - - - --- - - -~

Data Name : E:\GC-17 A\GC-D~~~\QN-VALIDATION\QN~VALID\~OO~O~\QN-O~.~C~
Method Name : E:\GC-1 7 A\GC-METHODS\QUINAPRIL-LF.gcm
Instrument no
Intensity - - --
2000000 --
W
5
/ sz
I
1500000- 1:I -
2
min
Peak Table- Channel -
~&.~ime --Nams - Area

10.156 N,P_TANB
.- 109 12240
11.580 ACETONE 857647 --
1 1 . 8 2 IPA 87159 --
_ 1 2 29 1 A C N 30496 -
14.386 DIPE -- a6214

I 5.697 _-ETHYUCET~TE 607
- -I22
21.006 JSLUENE _ 2 12053 --
Total . - - 1314_3431

BIN NUMBER : \ ~ q INSI'.NO. :AH/ADUOS

AARTl HEALTHCARE Lm.
o~
**$~O~VIBI~ONssasri ,h~<~s~ias sz
iwi-r 3
Sample Information
Analysis Date & Time : 8120120059:24:19 PM
User Name : Admin
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDAT10N\QN-VALID\2OO8O5\QNLO7.gcd
Method Name : E:\GC-17 A\GC-METHODS\QUINAPRIL-LF.gcm
Intensity - . . --
2000000 --
1
, IZ
-
2
4
20
min
Peak Table - Chamel 1

Peak# Ret.Tirne Name Area
1 10.057. N-PENTBNE _
120320_4-5_
2 1 1.488 ACETONE - 87_5265 --
3 11.789 IPA-
---- . . 78973
4 12.197 ACN .- 30033 -
5 14.290 DIPE- 462173 ..

6. . 15.607 E T H Y L ACE-TATE 604211 -
7 .20.975 TOLUENE - 251475 -
Total --
. .-. 14334175
-- .- .
PRODUCT NAME : QllfNAPRIL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER : ROBCISTNESS
BIN NUMBER : (1O INSI..NO. : AHIADLIOS
CHROMATOGRAM NAME :
DONE BY:
DATE : DATE :

QUINAPRU, HYDROCHLORIDE USP I
7.8.1-a.6 METHOD PRECISION:
The change in flow rate was determined by injecting two sample preparations from
the same batch - batch number - AH 105061108 and quantifying the solvents
present in the batch as well determining the % RSD of the area and concentration
of the solvents.
AH/0506/108, and estimating the content of residual solvents:
TABLE - 7.8.1-a.6-1
7.8.1-a.7 RESULTS:
Blank Chromatogram No.: 1 11

TABLE - 7.8.1-b.7-2
I M> ND ND ND ND ND ND 112
2 ND ND ND ND ND ND ND 113
I Acceptance
criteria I NMT 15.0%
Page 59 of 82

TABLE - 7.8.1-a.7-2
Acceptance
NMT 15.0%
criteria

1 . The area for n-Pentane, acetone, isopropyl alcohol (ZPA), acetonitrile (ACN),
7.8.1-a.9 CONCLUSION: Meets the acceptance criteria for method precision
7.8.1-a.10 CHROMATOGRAMS: Chromatograms are given on the following pages.
Back to top
Page 60 of 82

dl?! T)l%lC;tC.R 0 1 'RE1 Tt 'NDt,5T$E"; ibpi-' 1
Sample information
Analysis Date & Time : Sl201200510:07:1 1 PM
User Name : Admin
Sample ID : BLANK ( Flow = 1.53rnUmin)
Data Name : E:\GC-17 A \ G C - D ~ ~ ~ \ Q N ~ V A L ~ D A T I O N \ Q N ~ V A L I D \ ~ O O ~ O ~ \ Q N ~ O ~ , ~ C ~
Method Name : E:\GC- 17 A\GC-METHODS\QUINAPRlL-LF.gcm
intensity
2000000
min
PRODlJCT NAME :QUlNAPRlL HCL RESIDUAL SOLVENTS VALlDATlON

PARAMETER :ROBllSTNESS
BIN NUMBER : II 1NST.NO. :AH/ADWOS
DATE :

AAR71 HEALTHCARE MD.
&PI WIYISW3h O F A & H T * 1 % i l Z k d 4 i i P ..iNt'Ij
Sample Information
Analysis Date & Time : 81201200510:49:55 PM
User Name : Admin
Sample ID : SAMPLE 1 ( Flow = 1.53mlJmin)
Data Name : E:\GC- I7 A\GC-Data\QN-VALIDATiOMQN-VALID1200805\QN~09.gcd
Method Name : E:\GC- I7 A\GC-METHODS\QUINAPRIL-LF.gcm
Intensity
2000000
min
PRODllCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

$IN NUMBER : 112 1NST.NO. :AHIADLIOS
DATE :

Sample information
Analysis Date & Time : 812012005 1 1 :32:48 PM
User Name : Admin
sample ID : $AMPLE 2 ( Flow = 1.53mlimin)
Data Name : E:\GC- I7 A\GC-Data\QN-VALIDATION\QN-VALID\200805\QN
I O.gcd
Method Name : E:\GC-17 A\GC-METHODS\QUTNAPRIL-LF.gcm
Intensity
2000000-
min
Peak Table - Chamel 1

PARAMETER : ROBtISl7WESS
BIN NUMBER : ' . 'INSI'.NO. :AH/ADWOS
DONE BY:
DATE :

QTJINAPRIL HYDROCHLORIDE USP
7.8.1-b FLOW RATE +lo%

SYSTEM PRECISION
Back to top
Page 61 of 82

r
QUINAF'RIL HYDROCHLORIDE USP
7.8.1-b Flow rate change 1.87 mumin
flow rate (* 10%)and comparing the results, as well as analyzing the same sample.
7.8.1-b.1 STANDARD SOLUTIONS PREPARATION:
7.8.1-b. 1.1 Blank: N,N dimethyl formamide was used as blank.

7.8.1-b.1.2 Diluent: N,N dimethyl formamide
7.8.1-b. 1.3 System suitability solutions:
manner:
TABLE - 7.8.1-b.1.3 -1
Page 62 of 82

7.8.1-b.2 RESULTS:

TABLE - 7.8.1-b.2 -1
- -
Acceptance
criteria NMT 2.0%
TABLE - 7.8.1-b.2 -1
Average 1 39713459 1 2814372 1 259646 1 85793 1 1554040 ( 1926762 1 393670 1
Acceptance
criteria NMT 15.0%
Page 63 of 82

QuINAPRrL HM)ROCHL,OFUDE USP
7.8.1-b.3 INFERENCE:
1. The %I RSD of retention time was 0.26 to 1.14.
7.8.1-b.4 CONCLUSION: Meets the acceptance criteria for system precision.

7.8.1-b.5 CHROMATOGRAMS: Chromatograms are given on the following pages
Page 64 of 82

AARTI HEALTHCARE LTD,
APE U L < 1 5 a l e 0 6 .4AY-il~4LA!5iTFlii 'ir :IS1 7E:j
Sample Information
User Name : Admin
Sample ID
Data Name
-
: BLANK ( Flow 1.87 mllmin)
: E:\GC- 17 A\GC-Data\QN-VALiDATION\QN-VAL1D\200805\Q
I .gcd
Method Name : E:\GC- I7 A\GC-METHODS\QUINAPRIL-HF.gcm
Instrument n o : AHIADLIO5
Intensity
2000000
min
YRODIJCT NAME : QUINAPRIL HCL RESIDIIAL SOLVENTS VALIDATION

PARAMETER : ROBIJSTNESS
BIN NUMBER :

AARTl HEALTHCARE LTD,
RPI MViM3N O* &M+Tgi+irlOlS-SYR.tS ..rMll il t r
Sample Information
Analvsis Date & Time : 8/21/200512:58:27 AM
usehame : Admin
Sample ID : 100% STD ( Flow = 1.87 mllmin)
Data Name : E:\GC- I7 A\GC-Data\QN VAL1DAT1ON\QN~VALID\20080S\QN~1
2.gcd
Method Name : E:\GC-17 A\GC-METHODS\QUINAPRIL-HF.~C~
2Intensity
000000~ -- - - -- --
20
min
. .
Peak Table - Channel 1 - -. -. -
Peak# Ret.The- Name--

- - --Area - --Area%--
-
--I 7.912 N-PENTANE 1 --40590655 -- 25.1163

-
-
2' 9,226 ACETONE - 2838918

- -
5.9531 -
3 9.558 I P A 261658 0.5487

. 0.1843
4 9.869 ACN 87908
5 1 1 3 6 6 DEE - _- 1555472 3,2611
6 13.117 ETHJ-L ACETATE UXL3408- - 4.1 112 -
7 - 18.737_-TOLUENE ..
-
,. 390441-- - 08182-
Total - - - --
--
, 41688460 100,0000 -

BIN NUMBER : \\< 1NST.NO. :AWADW05
CHROMATOGRAM NAME :
DONE BY:
DATE : DATE :

Sample Information
Analysis Date & Time : 8/21/20051:41:13 A M
User Name :Admin
~am~le~ame : QUINAPRIL
Data Name : E:iGC- I 7 A\GC-Data\QN-VAtlDATION\QNNVALID\200805iQNN1
3.gcd
Method Name : E:\GC- 17 AiGC-METHODS\QUiNAPRIL-HF.gcm
Intensity
2000000 - -
- -.
Peak Table - Channel 1 - -
~eak#~. eTt ~ YN- a m e - -- Area
---
,
1
2
-1 7.903 N-PENTANE
9 . 2 1 6 .ACETm-
I 41035229 -
2834075 -
--
-
Area% --
13.6659
0.9438
_,
3 I 9.551 ,IPA 2 5 8 1 3 9 0.0860 1 +
--4 + -9.856 ACN .. 3-

. 16- -- 0.0282 -
5 11.856 DIPE
--- --
1591074 0,5299-- -
- 6 13.108 , ETHYL ACETATE; 1E!5L2RL p- 0.6498 -
7 18.731 T O L U E N E .. , 391860 0.135 _ -
-.- 8
Total
20.788
--
- -
p
-
L
-- 25212671 5
300274693
-
-
.
- 83.9654
--
100.OOOOp
--

BIN NUMBER : I\C MST.NO. :AHIADWOS
I CHROMAT0GRA.M NAME : +anmi$. 2
DONEBY: & CklECKED
DATE: 2 ~ 1 8 1 ~

Sample Information
Analvsis Date & Time : 812 1/20052:24:01 AM
~seri\lame : Admin
Data Name : E:\GC- I 7 A\GC-D~~~\QN-VALIDATION\QN~VALID\~~O~O~\QN-~
4.gcd
Method Name : E:\GC-I 7 A\GC-METHODS\QUINAPRIL-HF.gcm
lnstrument no : AWADLIOS
Intensity --
2000000
LL!
Z
0
'Vs
5
20
min
P& Tablfiharpel 1 . .
pk;# ~ e f . ~ i m e -- Name
- .- Area . Are&
1 7,765 N-PENT~NE _ 39g9759 84.4906
2 9.010 ACETONE - _ 2882429 -6.1920
.
3 9.387 -1PA 277637 0.5954

4 9.713 ACN -- 90125.-- 0.1933 -
5 11.782-DIPE 1563890 .3.3537
6 S T H E ACBAE~ 30045~ , 4.2899

.- -
7 ,.18.718 TaLUENE - - 412782 _- ..-, _ 0.8852

-
_Total - .
. 46632 123
-
_ 100.0000
PRODUCT NAME :QULNAPRIL BCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :ROBIISTNESS
BIN NOMHEI<: 11 7 A INST.NO. : AHIADUOS
CHROMATOGRAM NAME :
DATE :

Sample Information
~se<~arne : Admin
Sample ID : 100% STD ( Flow = 1.87 mlirnin)
Data Name : E:\GC- 17 A\GC-Data\QN~VAL1DATIO~QN~VALID\200805\QN~l5.gcd
Method Name : E:\GC- 17 A\GC-METHODS\QUINAPRIL-HF.gcm
Intensity
2000000- - --
min
- --
Name
7-
1-
- - -
A r e a
_-
Areao% .
_-
Peak# Ret.Time, - -
--,
- --
, -
L. - 7.912
- N-PENTANE - 39270109 84.702T _-
-
- -
2 -. 9.223 ACETONE - 1 -- 2837981 -

_- 6.1213
3 -.9.556 IPA - - 267764 -
-. 0.5775 -
4 9.862 ACN- - - 93300 0320

5 11.862 DIPE - _ 1533146 - 3.3069-
6 - ~~J~~_--ETHYL,_ACETATL --_193013!- - 4.1632 -
7 _-I 8&09 TOLUENE- - 424830

-
-_ 0.9163.
~ 3 1 - - --
-
L 46362261 -100.0000
-
PRODUCT NAME : QUINAPRIL HCL RESlDUAL SOLVENTS VALUIATION

BIN NUMBER : 1\ & INST.NO. :AHIADLIOS
I CHROMATOGRAM NAME :
DONEBY: - CHEC
DATE : ~rl\$kK DATE

Sample Information
Analvsis
.. Date & Time : 812 1/20053:49:42 AM
usehame : Admin
Sample Name : OIIINAPRIL
Sample ID I TO& STD ( Flow = 1.87 mllmin)
Data Name : E:\GC-17 A\GC-Data\QN VALIDATION\QN-VALIDDO0805\QN_
I6.gcd
Method Name : E:\GC-17 A\GC-METHO~S\QU~NAPRIL-HF,~C~
Instrument no : AH/ADWOS
Intensity .- -- -
2000000 -
--
- - .. -- . - - -
. . . !. . -
.
..- -. .. ---- .
-- .
0 . - ~ .-
, - -- - -- . -
- . .... -
0 10 20
min
-
~eakxableshan& 1
P&# .~et.%me, ~ a e m Area - - ~iea%
7.920 a - P B A I A N E --- -
I
--
38404m
- -_ _ - 85.1768
9 . 2 z AGTONE
2 -- -- - 264Q106 5.9676
-
-9.562 IPA 236667 0.5249

-
-- -
4- 9.873 ACN-
- - -- 6 5 8 7 9 - 0.1461 -
5 11.864 DIPE 1.5562 - 3.35AO
6 I~.~~~_-ET~_L~*T -
E1_818= - 4.0 3-24
7 18.730 TOLUENE - 359763 0.7979
Total - - 45088233 !@.OOOO

BIN NUMBER : \\q 1NST.NO. :AHIADWOS
CHROMATOGRAM NAME :
DONE BY:
DATE : 9 41 do5

Sample Information
.
1 Tw-r Name : Admin
Sample Name
Sample ID
.--~
. 01JINAPRIL
~~
: 100% STD ( Flow = 1.87 mllmin)

Data Name : E:\GC-I7 A\GC-Data\QN-VALIDATION\QNNVAL1D\200805\QN17.gcd
Method Name E:\GC- I7 A\GC-METHODS\QUNAPRIL-HF.gcm
20
min
Peak Tab& - C h ~ I l --
--
_~eak_#--~et.~ime~ N a m ~ .
_- Area Area%
1 _- 7.795 ._,N-PENTANL - 39580275-
- - 84.9952_.__
--
2 9.034 ACETOKE .
. 2797023_ 6.0065 -
3 . 9.352 [PA 256008 --
0.5498
4 -9.640
-. _ACN 86228 4.1852
5 11.710 DIPE - - 1568396
- 3.3680
-- --
.- 6 13.022- ETHYL A C E T A ~. ~ 1 8 9 7 0 6 6
- --
4.u3 .
7 1_8,695 TOLUENE 3823& - 0.821 1

Total - -- -. 46567340 100.0000..

BIN NUMBER : 1 20 1NST.NO. :AHtADLfOS
CHROMATOCRAM NAME :
DONEBY: 6
DATE : DATE :

7.8.1-b.6 METHOD PfWCISION:
the same batch - batch number - AH /0506/108 and quantifying the solvents
of the solvents.
Content % RSD - NMT 15 .O%
AH105061108, and estimating the content of residual solvents:
TABLE - 7.8.1-b.6-1
7.8.1-b.7 RESULTS:

TABLE - 7.8.1-b.7-1
Page 65 of 82

QUINAPRIL HM)ROCHLORIDE USP ,
TABLE - 7.8.1-b.7-2
Acceptance
criteria NMT 15.0%

1. The area for n-Pentane, acetone, isopropyl alcohol (IPA), acetonitrile (ACN),
7.8.1-b.9 CONCLUSION: Meets the acceptance criteria for method precision
7.8.1-b.10 CHROMATOGRAMS: Chromatograms are given on the following pages.
7.8.1-b.11 COMPARISON OF PRECISION AND ROBUSTNESS:
The comparison of % RSD for Area and retention time is given in the following
table;
Page 66 of 82

- -
I
Back to top
--
Page 67 of 82

Sample Information
Analysis Date & Time : 8/21/20055:15: 18 AM
User Name : Adrnin
Sample Name : QUINAF'RIL
Sample ID : BLANK ( Flow = 1.87 ml/min)
Data Name : E:\GC- 17 A\GC-Data\QN-VALIDATION\QN-VALIDV00805\QNI
8.gcd
min
PRODUCTNAME :QUlNAPRlL HCL RESIDUAL SOLVENTS VALIDATION

I PARAMETER :ROBUSTNESS I
I BIN NUMBER: 12 1 1NST.NO. :AWADUOS I
CHROMATOGRAM NAME :
&
DONEBY:
DATE : a CHECKED BY:
DATE :

Sample Information
aAARTl HEALTHCARE LTD.
BPS iWvlJ1Dfu W M R I I sWDldSW4ES ,IhBI*Ctj
Analysis Date & Time : 8121120055:58:05AM

User Name : Admin
Sample ID : SAMPLE I ( Flow = 1.87 ml/rnin)
Data Name : E:\GC-17 A\GC-Data\QN-VALIDATION\QN-VALID\200805\QN-I
9.gcd
Intensity
2000000-- - ---
20
min

BIN NUMBER : \ 22 INST.NO. :AWADLIOS
CHROMATOGRAM NAME :
DONEBY: 6
DATE :

Sample Information
Analysis Date & Time : 8121/20056:40:57 AM
User Name : Admin
Sample Name -: OIJINAPRIL
x - -- - -
Sample ID : SAMPLE 2( Flow = 1.87 rnlimin)
Data Name : E:\GC- I7 A\GC-Data\ON VALIDATION\QN VALID\200805\QN 20.gcd
Method Name
Instrument no
Intensity
2000000
min
PRODUCT NAME : QUINAPRLL HCL RESIDUAL SOLVENTS VALIDATION

BIN NUMBER : 1NST.NO. : AHIADUOS
CHROMATOGRAM NAME :
DONEBY: &- CHECKEDBY:
DATE : MI&<

I pp
- -
1
-
QUINAPRn, HYDROCHLORIDE USP
7.8.2 CHANGE IN INCUBATION TIME 20%

7.8.2-a INCUBATION TIME -20%
SYSTEM PRECISION
Back to top
Page 68 of 82

QUlNAPRIL HYDROCHLORIDE USP
7.8.2-a Incubation time change 16 min
Robustness was carried out by checking the system suitability by changing

incubation time (*20%) and comparing the results, as well as analyzing the same
sample.
7.8.2-a.l STANDARD SOLUTIONS PREPARATION:
7.8.2-a.1.l Blank: N,N dimethyl formamide was used as blank.

7.8.2-a.1.2 Diluent: N,N dimethyl formamide
7.8.2-a.1.3 System suitability solutions:
manner:
TABLE - 7.8.2-a.1.3 -1
Page 69 of 82

QUINAPRIL HYDROCHLORIDEUSP
7.8.2-a.2 RESULTS:

TABLE - 7.8.2-a.2 -I
5 8.830 10.194 10.513 10.864 12.898 14.173 19.684 129

6 8.807 10.168 10.492 10.841 12.879 14.155 19.670 130
Average 8.902 10.270 10.590 10.942 1 2.982 14.258 19.752
SD 0.066 0.070 0.069 0.070 0.074 0.075 0.060
%RSD 0.74 0.68 0.65 0.64 0.57 0.52 0.30
Acceptance
criteria NMT 2.0%
TABLE - 7.8.2-a.2 - 2
Average 1 14400525 ( 1029921 1 95578 1 33402 1 560031 ( 715124 ( 152918 (
NMT 15.0%
Page 70 of 82

7.8.2-8.3 INFERENCE:
1. The % RSD of retention time was 0.30 to 0.74.
7.8.2-a.4 CONCLUSION: Meets the acceptance criteria for system precision.
7.8.2-a.5 CHROMATOGRAMS: Chromatograms are given on the following pages

2 125 100% STD-I (System precision)

Page 71 of 82

QUINAPRIL HYDROCHLORIDE ISSP
7.8.2-a INCUBATION TIME +20%

SYSTEM PRECISION
Back to top
Page 74 of 82

Sample Information
1-lser
... Name
. ... : Admin
Sample Name
Sample 1D
. .---------
: BLANK ( incub time=16min)
Data Name : E:\GC-17 A\GC-Data\QN-VALIDAT10N\QN-VALlD\200805\QN2I
.gcd
Method Name : E:\GC- I7 A\GC-METHODS\QU iNAPRIL.gcm
Intensity - - -- -- -- -
2000000
min

BIN NUMBER : \2q 1NST.NO. :AH/ADL/OS

Sample Information
Analysis Date & Time : 8/21/20058:13:35AM A
User Name : Admin

Sample ID : 100% STD ( incub time=16min)
Data Name 17 A\GC-D~~~\QN-VALIDAT~ON\QN-VALIDVOO~O~\QN-~~.~C~
: E:\GC-
Method Name : E:\GC-17 A\GC-METHODS\QUINAPRlL.gcm
Intensity
2000000
min
PeakTele-- Channel 1 - .
&&# R Z T ~N a m
~e - - -A~a- - -
Areayo
- r- 8.940.- N P E N T A N E - -16617541 - -
846281 .
-2
- -
- 10.305 ACETONE - A - -2a543 - - +

6.1543
-
-
3 10~521IPA- -
.
-
112181-
-
_ 0.5713
4 - NJ.gfpecN_ - - 367B - -
0.1 869 _.
5 13.011 DIPE-. 647529

- -- -
3.2977
6 14,286 ETHYL ACETATE . 836408 4.2594
r 19.~35 T . O L _ U E N E - 1 7 7 ~ 7 -
19635913
-
- -
-
0.90 17
13&00_00
Total . - -
PRODUCT NAME : QUINAPRIL HCL RESIDUAL SOLVENTS VALlDATlON

BIN NUMBER : I2 5 1NST.NO. :AH/ADL/OS
CHROMATOGRAM NAME '
DONE BY: . CHECKED.

DATE : P~\u\D<

Sample Information
Analysis Date & Time : 8121120058:53:57 AM
userkame : Admin
Sample Name : QUINAPRLL
Data Name : E:\GC- 17 A\GC-Data\QN VALIDATION\QN~VALID\200805\QN-23.gcd
Method Name : E:\GC- 17 A\GC-METHOBS\QUINAPRIL.gcm
Instrument no : AHIADLJOS
Intensity .. --
2000000 -
min
-- --
Peak Table- Channel 1
-
-
peak# & t . ~ i m e Name_ -- Area - - -

&a% .
.
1 . 8.9Q N-PEBTANE 17532480 -. 858178

2 1031 1 ACETONE. 1153574 5.6465
3
4_
-10.626 I P A
10.985 ACN _-
.-
-
.-
-
100004.-
35465- - -
-
-
. .
.
0.4895 -.
0-. 1 7 3 6 -_
5 - - - BlPL --
13.028
, . -
---
-
670961
-
-
- -
-
- 3.2842
6 14,307 _ETHYLACETAT& -786426 - - 3.84_94 -
--7 19.793 T O N I E N E -. 150990- 0,7391
TO^ -. . 20429900
-
l00.0000

PARAMETER : ROBIISTNESS
BIN NUMBER : 126 INST.NO. :AHIADLIOS A
CHROMATOGRAM NAME :
DONE BY:
DATE: +A\$?\& DATE:

AARfl HEALTHCARE LTD.
ar*il a f V ~ * l $ #a)l~ I B U fi tBB?L'Y:tR'r ' ddLmB-f
Sample Information
Analysis Date & Time : 8121120059:34:52AM
user-~ame : Admin
Data Name : E:\GC-17 A\GC-Data\QN-VALIDATION\QN-VALlD\200805\QN-24.gcd
min
- - - - -- _ - - -
Peak Table - Channel 1 - - -
Peak#. &.Time- urn~ - Area ..

- -
AS~%
84.5642
I_ 8.960 N-PENTANE- _ - 1358x89 .
-
--2
-
10.328ACLTONE - - -981705 - .- - 6.1_123_

0.6036
3 _ _ 10.653 P A _ --
- -- 96952- -. .-
4- - I 1 ~ 0 i K N - 34708 0_216_1
5 13.055 DlPE 527784 3.2861
6
-
1_4.33_0 ETHYL ACETATE .-691811- 3.3074
7-
-
_ 19.812 TOLYENE - - -146191-

- - -0.9102 - -
Total -_ - - -- - - --16061046 - ~ o d o o ~ -

BIN NUMBER : 1 INST.NO. :AWADLm5
CHROMATOGRAM NAME :
DONE BY: & CHECKEDBY
DATE :

fieit IlrWf410N C)* r i A H P i :Wf>iiDTW" % iWr'W,
Sample Information
user-~ame ; Admin
Data Name : E:\GC- I7 A\GC-D~~~\QNVALIDATION\QN-VALID\~OO~O~\QN-~~.~C~
Method Name : E:\GC- I7 A\GC-METHODS\QUM APRIL.gcm
Intensity ..
2000000 -
-
Peak
-- Table- Channel 1 -
peak# ~&.Time Name . Area-
- - Area%
1 . 8.932 N-PENTANE - 120694 14 84,4884
--
---
.
2 l.301 A B T O N E - -898684 - 6.2~0
3 10.627.- IPA -- -- 73932
- - +
0.5 171
4 . 10.983 ACN -.- 2 564P - .- 0.1795
_ 5- 13.023__D! -- 413491
--
- 3.3 L46
--6 14.298 ETHYL AaTALE, --.621462 -- 4.3504
-
7 -19.787 T O L U m E . 122616
+ ..- 0.8583
T&I _ - - -14285252
- 100.00_!0 -

PARAMETER : ROBlJSTNESS
BIN NUMBER : (2.6 INST.NO. :AWADW05 ,,

Sample Information
User Name : Admin
Sample ID : 100% STD ( incub tirne=16min)
Data Name : E;\GC-17 A\GC-Data\QN VALIDATION\QN-VAtlD\200805\QN3.gcd
2Intensity
000000 - --
20
min
Peak N l e -Channel 1
- .
Peak# Rec~irnY- Name- Area - Area%

1 .
- 8830- N-PENT_ANE 13269803 .
--
84.9926
2 -- 10L94 A C E T O N E - - 926170
- .
5.9359
i 10.513,IPA
- _- I - -89837 -. 0.5754
4 - 10.864 ACN -- -- 30079 -. 0.1P27
5 - 12 . 8 9 L D I H 5
- 507904 3.2531
6
- 14.173 , ETHYLACE-UTE -640606 - 4.1031 .-.
7
-- 19.684 TmUENE
-
-- - 147897 -- - 0.9473 __
Total - -- ---- 15612900 -. - 1o!.ooo~

BIN NUMBER : 1 4 INST-NO. : AWADLIOS
CHROMATOGRAM NAME : ~'11-
_
&
DONE BY:
DATE; : .~\s\o<
CHECKED BY :

AARf l HEALWARE LTD.
API D&LSiUh Or digfit?fSIBI15114IP 5 -8FPI-P
Sample Information
~ s eamer ~ : Admin
Data Name : E:\GC- I7 A\GC-Data\QN-VAtlDATION\QN~VALIDVO08O5\QNN27.gcd
Method Name : E:\GC- 17 A\GC-METHODS\QUINAPRILgcm
Intensity -. --
2000000 -
--
rnin
--- --
--
-
- -
Pe&# Ret.Time _Name - -- Area

- - - Area%
1 8 8 0 7 N:PEN_TAN_E 13332010
- - -
83.84%
2 10.168 ACETONE .- - 10-14248 - . 6.3-538
3 10.492 IPA 1Om4 0.6325

4 10841 ACN . 37806 -
0.237_8
5 - 12879 DIPE . 532510 -
-
-3.349 1
- 6 - 1 4 ~ _ETHYLACE_TATE+
5 7Hr.19- - 4,4901
- 7- 1 9 . 6 3 TOLUENE .. - 1 7 2 7 5 8 .-
-
1.0865
Taal-
-
-
- _ - - - 15 8 9 9 g 5 _
- -
l _ o o . ~ ~ -o o
PRODUCT N A M E : QlJJNAPRlL HCL RESIDUAL SOLVENTS VALIDATION

PARAMETER :ROBCJSI'NESS
BIN NUMBER : 1NST.NO. :AH/ADWOS ,
,
CHROMATOGRAM NAME :
DONE BY: A CHECKED BY :
DATE : DATE :

7.8.2-a.6 METHOD PRECISION:
The change in incubation time was determined by injecting two sample

preparations from the same batch - batch number - AH /0506/108 and quantifying
the solvents present in the batch as well determining the % RSD of the area and
Content % RSD - NMT 15 .O%
AH /0506/108, and estimating the content of residual solvents:
TABLE - 7.8.2-a.6-1
7.8.2-a.7 RESULTS:
TABLE - 7.8.2-a.7-1
1 ND ND ND ND MI ND ND 132
Acceptance
criteria
NMT 15.0%
Page 72 of 82

- - -

QUINAPIUL HYDROCHLORIDEUSP
J
TABLE - 7.8.2-a.7-2
Average NA NA NA NA NA
NA NA NA NA NA
Acceptance
criteria NMT 15.0%
1. The area for n-Pentane, acetone, isopropyl alcohol (IPA), acetonitrile (ACN), di
isopropyl ether (DIPE), ethyl acetate and toluene was not detected in sample.
7.8.2-a.9 CONCLUSION: Meets the acceptance criteria for method precision
7.8.2-a.10 CHROMATOGRAMS: Chromatograms are given on the following pages.
Back to top
Page 73 of 82

a
AAFZtl HEALTHCARE LTD.
nl"i In?iir3h UJ &&A rr ~BIJLP.T~IE'~
W-F
Sample Information
Analysis Date & Time : 812112005 12: 14:Ol PM
User Name : Admin
Sample ID
Data Name
Method Name
instrument no
Intensity
2000000 - - - --

1 PARAMETER :ROBUSTNESS
- --
DATE :

AARn HEALWARE LTD.
&PI DIYlSlPrPd LY AAMTI rti.lli!SlbO:iTS t6UrTD
Sample Information
Analysis Date & Time : 812 112005 12:54:48 PM
User Name : Admin
sample Name : QUINAPRIL
Sample ID : SAMPLE 1 ( incub time=16min)
Data Name : E:\GC- I 7 A\GC-D~~~\QN-VALIDAT~ON\QN-VALID\~~O~O~\QN-~~.~C~
Method Name : E:\GC-17 A\GC-METHODS\QUn*IAPRIL.gcrn
Intensity
- -. - - - .- -. --. .. ... -.
2000000 ~ - - -- -p ~~ --
..
0 : . .
_ .
- .
.
. .
-
-
.
- .
_~ - -
-
7
-
---
-- -- -
-
.--
,- - -- - ... -
0 10 20
min
-
PRODliCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

BIN NUMBER : '3 INST.NO. :AHIADUOS A
CHROMATOGRAM NAME -
DATE :

ad* TEy i i i i t r r C 1 d A R i rUD* bVit.l + -aVr-- '
Sample Jnformation
Analysis Date & Time : 8121/20051:35:39PM
User Name : Admin
Sample [D : SAMPLE 2 ( incub time=l6min)
Data Name : E:\GC- 17 A\GC-Data\QN VALIDATION\QNLVALiD\200805\QN-3O.gcd
Method Name : E:\GC-I 7 A\GC-METHO~S\QUINAPRIL.~C~
Intensity
2000000- -
20
min

BIN NUMBER : 133 1NST.NO. :AWADLlO5
CHROMATOGRAM NAME.
DATE :

QUINAPRIL HYDROCHLORIDE.USP
7.8.2-b Incubation time change 24 min
*
incubation time 20% and comparing the results, as well as analyzing the same
sample.
7.8.2-b.1 STANDARD SOLUTIONS PREPARATION:
7.8.2-b.1.l Blank: N,N dimethyl formarnide was used as blank.

7.8.2-b.1.2 Diluent: N,N dimethyl formamide
7.8.2-b. 1.3 System suitability solutions:
manner:
TABLE - 7.8.2-b.l.3 -1
Page 75 of 82

QUINAF'RIL HYDROCHLORIDE USP
7.8.2-b.2 RESULTS:
Blank Chromatogram No.:134
TABLE - 7.8.2-b.2 -1
Acceptance
criteria
NMT 2.0%
TABLE - 7.8.2-b.2 -1
Average 13 148572 967467 97240 3 2703 515091 677964 151748

SD 1 15 1 199.861 74430.249 4412.781 284 1.647 449 16.572 56928.258 18674.087
%RSD 8.76 7.69 4.54 8.69 8.72 8.40 12.3 1
Acceptance
NMT 15.0%
criteria
Page 76 of 82

1. Tbe % RSD of retention time was 0.26 to 1.14.
7.8.2-b.4 CONCLUSION: Meets the acceptance criteria for system precision.
7.8.2-b.5 CHROMATOGRAMS: Chromatograms are given on the following pages

Page 77 of 82

Sample Information
User Name : Admin
sample Name : QUINAPRIL
Sample ID : BLANK ( incub time=24min)
Data Name : E:\GC- I7 A\GC-D~~~\QN-VALIDATION\QN_VALID\~O~~O~\QN~
I .gcd
Method Name : E:\GC- 17 A\GC-METHODS\QUINAPRlL.gcrn
Instrument n o ; AHIADLIOS
.
-, , - .
0- . -.
_- -
- ...
.
_
-.
.- --
-
-. . . . - .. . ~ .
0 10 20
min

PARAMETER :ROBllSTNESS
BIN NUMBER : b3 4 INST.NO. : AHIADLIOS
CHROMATOGRAM NAME '
WNEBY:
DATE : DATE :

AARTl HEALTHCARE LID.
irpi ibrLii,iDb! 31-A A L I I rPBU*aSTR!P$ . iW2-eb'
Sample information
Analysis Date & Time : 8/21/20053: 16:44 PM
usehame : Admin
Sample ID : 100% STD ( incub time24min)
Data Name : E:\GC- 17 A\GC-Data\QN VALIDATiON\QN-VALID1200805\QN-32.gcd
Method Name : E:\GC- I7 A\GC-METHO~S\QUINAPRIL.~C~
Intensity
2QOOOOO .- - - - -- - - _ W
z
- -
-- -
2
ti4.
F
min
- - - - -Peal-TabJe - s h a z e l l -
-
Area%
Pea#k ,Ret,Time -- - -Are2 -
. _I -- 8.795 ,
-
N-PENTAN! -_ - 1 3 436u - 84.2215
_ 2 10.159 ACETaNE 999164 -
6.2535
3
- _ 10.486 IPA- -
97207
- - --
- .0.6084.-
0.205 1
4 l0.824-.A~ - - --32716 - -
5 u.868 ,DIE - 530370 -

3.3 195
6
.- --
14,143 ETHYL ACETATE_ 692291 - - 4,3328
19.666 TOLUENE- , -1e2I-5- -- -
1.0591-
Total -- -.
- - -- - -
15972633 ,- -
100!000 -
1 PRODUCT NAME : QUINAPRIL HCL RESIDUAL SOLVENTS VALIDATION

I
BIN NUMBER : \3'C INST.NO. :AHIADLIOS /7
CHRoM.4ToCRAM NAME : ~710 %' 1
DATE : DATE :

Sample Information
User Name : Admin
Sample ID : 100% STD { incub time=24min)
Data Name A\GC-Data\QN2VAL1DATION\QN~VALIDVO0805\QN-33.gcd
: E:\GC-17
Method Name : E:\GC-17 A\GC-METHODS\QUR\IAPRIL.gcm
Instrument no : MADL105
Intensity - - - -
2000000 - -
"
9
\D
w
V,
0.
' I ! . . .
min
- - -
- Peak-Table - Channel 1
-
PSak# Ret.Time - _Name -. -

-
Area -
--
__ Area% -
1 _ 8-94]
- N-PENTANE _ -11721338- -- 84.8282
-
- -
- 2 10,312 ACETONE--+- - 828632

- - 5-9959 -
-
_ -10.634J!!& -- -
92055
--
- - - 0.6_661_
4- 10.983ACN - - -
29406 -
- 0.2128 _-
- -
-456469 33029
- 3 - - 13.@6.-DIPE - - - ---
- 4.0923 _ -
-. 6
14.296 ETHYL ACETATE,
-- 565560 -
-
--
7
-
u.768 TOLUENE ,
- 124_63K - 0.9018-
Total - - - -
13820095 . lOO.O@lO
PRODUCT NAME : QUINAPRlL HCL RESIDUAL SOLVENTS VALIDATION

BIN NUMBER : INST.NO. :AWADLIOS

Sample Information
User Name : Admin
Data Name : E:\GC- I7 A\GC-Data\QN~VALIDATtO~QN-VALIDV00805\QN-34.gcd
Method Name : E:\GC- 17 A\GC-METHODS\QUINAPRfL.gcm
Instrument no : ANIADLIOS
Intensity
2000000 -- - - - -- -
20
min
- - - PeeTable -Channel 1 _
~ e & # -Ret.Time -_Name - - - - -_
Area - &ea%
8.950 N-PENTANE- 14243392 _ 84.6849
1 .. -
- -
-
2 10.322 -ACETONE -- -1020867 - 6.0696

1 10.645 L P * 95601 . 0.5684
-4 10...3p_ACN - -- , - 36Y41- -- -OA9& -
- -
5 33.027 DIPE - 1 - 5563636 -- - -- 3.3s11
-- 6 -14.303 E T H Y L A C E I A T E 1 - 7 D S 6 - I - -
4.2233
--
-_
- 7- -19.798 - TOLUENE-. A - g 8 3 6 -- 0.8830L
- --
- Total -- --
- - - 168_19286 .
-
130.0000
I PRODUCT NAME :QUMAPRIL HCL RESIDUAL SOLVENTS VALIDATION

1
d5
1NST.NO. : AWADWOS
CHROMATOGRAM N A M E : m 3
DONEBY: &" EHECKEDB
DATE : DATE : 2,

Sample Information
Analvsis Date & Time : 8/21/2005 5:18:45 PM
usehame : Admin
Data Name : E:\GC-17 A\GC-Data\QN VALIDATION\QN-VALIDV~O~O~\QN-~~.~C~
Instrument no : AH/ADLlO5
Intensity . - -
2000000- -- -
1000000 I W
r
<
I
z s
U
0 d W
t; A
P B
500000- U
2
0
tr
'a
2
W W
zz e-
0, - .
-
_ __ -
-
-
-
-
- - -
- -
.-
--
- ->
.
. - -
0 10 20
min
- .- -- - - P%xakT>blg- Chat@
- 1
peak# Ret.Timme NamL - - - - -- Areaoh
-
- -
1 - 8,795- NLPENTAQE 1 3427742

-- 84.20_60
--
2
-. 1o.t59_~cETONE- _ 985122- - 6.1778 -
3.. - 10.486.IPA _ - -99069-

- -
0.6213- -
-
4 _ 10.824 ACN -- 34635 - - -0.2172- - -
5 12.868 D E E - _ - -=3%7- - -- 3.2817

- -
6 B.143 ,ETHYL ACETATE^ 700469 - 4.3921 - -
- -
7
-
19.666 1 0 L U E N E -
- + - 175950
- --
lL1034 - -
TO& - - 15946294 130.0000. -
PRODUCT NAME :QUlNAPRIL HCL RESlDUAL SOLVENTS VALIDAT1m

1
BIN NUMBER : (3% 1NST.NO. :AHJADWOS
CHROMATOGRAM NAME.
DONE BY: -&- ' CHECKED BY
DATE : lug

Sample Information
User Name : Admin
Sample 1D : 100% STD ( incub time=24min)
Data Name : E:\GC- 17 A\GC-D~~~\QN-VALIDATION\QN-VALIDVOO~O~\QN~~~.~C~
Method Name : E:\GC- 1 7 A\GC-METHODS\QUINAPRIL.gcm
Instrument no : AH/AQL/OS
Intensity
2000000 - -
1000000 W
+
Q
W
z
t;
U
e 4
-1 W
500000 cS K?
>
6
z 55
$z :-; 5 P n
::
:
8
' 3 % 2 :
00
R
z
0 - - - -
.- - -
'2%
-- --
.
. 2 -- --
- -
-
0 10 20
min
Peak Table - Channel 1 .

. -
Peak# R A T & L - Name
-
8,950 'N-PENTANE - 14283219 -
I= - Area%
84.7142
- -
- 2 - 1- 0 . 3 2 2 ~ ~ ~ ~ 0 l ~
3 - - 10.645-F A 13
:@-
4 4 O 2~7 9 7 2 ~ - --._ 6 . 0.6218
-
Q969
-
-
4_ -10.993 ACN - -- 29917 - --

0.1774
- -
--5 13.02T ,DIPEL - - -- 552561 -

-
1.2773
6 14&03 ETHYLACETATE -72mo8 -- - 4__2734-
7 19.798 -TOLUEKE 141458
.-
0.8390
-
-30s . - - 16860474
- - I
100.0000

PARAMETER :ROBIISTNESS
1
BIN NUMBER : 1NST.NO. :AH/ADL/

AARTI WEALMCARE LTD.
A," 1ckZSIUtu (3r A a R r i R C l ~ ~ & " a l - ? ? $# f'bt
Sample Information
usehame : Admin
Sample ID : 100% STD ( incub time-24min)
Data Name : E:\GC-I7 A\GC-D~~~\QN-VALIDATION\QN-VAL~D\~OO~O~\QN-~~.~C~
Instrument no : AWADL/05
Intensity -- -- -- - - -- -
2000000- - - -- -
T et
I
4 -
I5
14
'I s
1500000 i3
CO
9
2:ui5 w
4
=
&
, zg< 9 0
oo,
' 8 8
s R
f
0 - -
20
min
- - Peak Table-Ch-l 1 .
Peak# &t.Time N- --. Area.-- -- Area%
1 8.965 N - J ~ T A N E 11757125 . 83.2603
2 10.334-[PA
- - ? - 943039 6.6783
3- 10.656 I P A - - 94666 -
0.6704
4 -- 11.000 ACN -. , 32538 - 0.2104
5- 1- 3 . 0 4 7 DIPE I - 462054 - 3.2874
6 14.320 ETHYLACETATE- 678631 -- 4.8059
7 - 19.755 TOLUENE -- 15Q119 .. 1,0673
Total - - - 142092_._ 100.0000

PARAMETER : ROBLISTNESS
BIN NUMBER : lw 1NST.NO. :AH/ADL/OS A
CHROMATOCRAM NAME : ST.D mi % +6

DONEBY: dC
DATE : ~ S \ O X DATE :

OUINAPRIL HYDROCHLORIDE USP I
7.8.2-b.6 METHOD PRECISION:
the same batch - batch number - AH /0506/108 and quantifying the solvents
of the solvents.
Area % RSD - NMT 1 5.0%.
AH /0506/108, and estimating the content of residual solvents:
-
TABLE 7.8.2-b.6-1
7.8.2-b.7 RESULTS:
Blank Chromatogram No.: 14 1

TABLE - 7.8.2-b.7-1
NMT 15.0%
Page 78 of 82

TABLE - 7.8.1-b.7-2
1. The area for n-Pentane, acetone, isopropyl alcohol (IPA), acetonitriie (ACN), di
isopropyl ether (DIPE), ethyl acetate and toluene was not detected in sample.
7.8.1-b.9 CONCLUSION: Meets the acceptance criteria for method precision
7.8.1-b.10 CHROMATOGRAMS: Chromatograms are given on the following pages.
7.8.1-b.11 COMPARISON OF PRECISION AND ROBUSTNESS:
The comparison of % RSD for Area and retention time is given in the following
table;
Page 79 of 82

RESIDUAL SOLVENTS - ANALYTICAL METHOD VALKDATION
1
Back to top
Page 80 of 82

Sample Information
Analysis Date & Time : 8/21/20057:2 1 :13 PM
User Name : Admin
Sample ID : BLANK ( incub time=24min)
Data Name : E:\GC-17 A\GC-Data\QN-VALIDATIOMQN~VALID\200805\QN-38.gcd
Method Name :E:\GC-17 A\GC-METHODS\QUINAPRiL.gcm
Instrument no : AWGDWOJ
Intensity
2000000 - --
- -- -
-. - .- -- --
min
PRODUCT NAME :QULNAPRIL HCL RESIDUAL SOLVENTS VALIDATION

BIN NUMBER : 14 1 INST.NO. :AHIADWOS
CHROMATOGRAM NAME :
DONEBY: 6 CHECKED B
DATE : 14 19lo<

A A R l HEALTHCARE LfD.
A*+ GNVl'sOM 6).&4Tt sHW>5'FRltS LlF%li+O
Sample Information
User Name : Admin
Sample ID : SAMPLE 1 ( incub time=24min)
Data Name : E:\GC- 17 A\GC-D~~~\QN-VALIDATION\QN-VALID\~OO~O~\QN~~~.~C~
Intensity - - -- - -
. -- -- --
2000000 -- - --
_ _ _-
.< <,
~,.
- -.
_
.
0 -_ . _.-- .._
- -
- _ -.
_.
- -
.
~-
~
. .
0 I0 20
min

PARAMETER :ROBllSrNESS
INST.NO. : AHIADLIOS ,
CHROMATOGRAM NAME : 5omP

Sample Information
User Name : Admin
Sample ID : SAMPLE 2 ( incub timee24min)
Data Name : E:\GC- I7 A\GC-Data\QN-VALIDATION\QNNVALID\2OO8O5\QNp4O.gcd
Method Name : E:\GC- I7 A\GC-METHODS\QUINAPRIL.gcm
Intensity
2 0 0 0 0 0 ~ ~---- - -- - - - --. - --
min
PRODUCT NAME :QUINAPRIL HCL RESIDUAL SOLVENTS VALlDATION

BIN NUMBER : 1 43
CHROMATOGRAM NAME :
DONE BY:
DATE :
&
ale<
.~lr
~
*
M 1NST.NO. : AHIADWOS
DATE : 2,
-

1
I1
INFERENCE
The G.C. procedure adopted for the determination of residual
solvents of Quinapril Hydrochloride meets all analytical method
validation criteria as per ICH guidelines for the quantification as
supported by the results summarised.
The results also establish that the method is sensitive, specific,
accurate, rugged and reproducible.
Back to top
Page 8 1 of 82

RESLDUAL SOLVENTS - ANALYTICAL METHOD VALIDATION
CONCLUSIONS
THE DATA AND RESULTS OF ANALYTICAL METHOD
VALIDATION OF RESIDUAL SOLVENTS IN QUINAPRIL
HYDROCHLORIDE INDICATE THAT METHOD IS
CAPABLE OF DETECTING AND QUANTIFYING
CONSISTENTLY THE RESIDUAL SOLVENTS PRES%NT
IN QUINAPRIL HYDROCHLORIDE
Back to top
Page 82 of 82

OPEN PART

3.2.S.4.4 BATCH ANALYSIS
The certificate of analysis of three validation batches QN-17020, QN-17022 and

QN-17023 of Quinapril HCl tested as per USP and in-house specification are
given on following pages.
Sr. No. Batch No. Manufacture date Batch Size

1 QN-17020 Jul 2017 85.90 kg
2 QN-17022 Jul 2017 85.10 kg
3 QN-17023 Aug 2017 85.40 kg
January, 2020 3.2.S.4.4 BATCH ANALYSIS Page 1

Facto ry : Unit - IV, Plot No. E - 50, MIDC , Tarap ur,
Taluk a & Distric t- Palgh ar, Pin - 40150 6. Maha ras htra,
INDIA .
Tel.: +91 89830 35452 , 89830 65452 , Tel efax: (02525 )
66109 2
QUIN APRI L HYDR OCHL ORID E USP
Form at No.: QA/FM -235/00
AR. No. : FG/0475/ 17 Date of Exp. : JUN-2022
Batch Qty. : 85.90 Kg Date of Release : 20/08/17
Sr.
TESTS RESUL TS SPECI FIC ATlON
No.
I. Descrip tion White powder A white to off-whi te powder, with pink cast at times.
2. Solubility Compli es Free ly Soluble in water.
3. Identification The Infrared spectru m of test sampl e should be concord ant
Compli es with simi lar prepara tion of that of Quinapril Hydroc hloride
a) By IR Spectru m WS/RS .
b) By HPLC Compli es Th e retention time of th e major peak in the chrom atogram of
assay preparation should be correspond to the chrom atogram
of th e standard prepara tion, as obtaine d in th e assay.
4. Specific Optical + 15.08° Betwee n+ 14.4° and + 15 .4° at25 °C on anh ydrous bas is.
Rotation
5. Water Conten t (By KF) 0.82 % w/ w Not more than 1.0% w/w
6. Residue on Ignition 0.05 % w/w Not more th an 0.1 % w/w
7. Conten t of Chlorid e 7.32 % Not less th an 7.2% and Not more than 7.6%
(By potentio metry )
8. Related Compo und 0.1 3 % Re lated Compo und A :NMT-0 .5%
(By HPLC) 0.05 % Re lated Compo und B :NMT-0 .5 %
0.06% Any unknow n impurity :NMT-0 .10%
0.31 % Total impurities :NMT-2. 0%
9. Assay 98 .91 % Not less than 98.5% and Not more than 101.5% on anh ydrous
(By HPLC) basis.
10. Residual solvent Not Detecte d Aceton e NMT 2000 ppm
(By HSGC) 25 ppm Acetoni trile NMT 410 ppm
Not Detecte d Di-i sopropy l ether NMT 700 ppm
32 ppm Eth y l Acetate NMT 3000 ppm
Not Detecte d Tolu ene NMT 890 ppm
Additio nal Test
1. I Palladium Content 4.1 0 ppm I Not more than 0.001 % (IO ppm)
Remark: The material complie s as per USP and above specification
.
Designee Mana ge
~---=-, ----- surance/
Quality Assurance Quality Assurance Quality Contro Designee
Note: Methy lene chlorid e is not used in the ma nufacturing process .
Precaution: Do the handlin g of materi a l unde r nitrogen gas because it is hi g hly
hygrosc opic in nature.
Storage: Store at tempera ture between 2 - 8 ° C
HEAD OFFICE :
71, Udyog Kshetra, 2nd Floor, Mulund Goregaon Link Road,
Mulund (W), Mumbai - 400 080. INDIA
Tel.: 00 - 91 - 22 - 67976666, 67976697, 25918195 •Fax : 00
- 91 - 22 - 25904806, 25653185 / 3234
Regd. Office : Plot No. 801/23, G.I.D.C. Estate, Phase - III, Vapi-3
January, 2020 Webs ite: www.a 3.2.S.4.4 BATCH ANALYSIS96195, Dist- Valsad , Gujarat, INDIA.
Page 2
arti-industries.com • CIN: L24110GJ1984PLC007301
AARTI INDUSTRIES LIMIT ED
Factory : Unit - IV, Plot No. E-50, MIDC, Tarapu r,
Taluka & District - Palghar , Pin - 401506 . Mahara shtra, INDIA.
Tel.: +91 898303 5452, 898306 5452, Telefax : (02525) 661092
CERT IFICA TE OF ANAL YSIS
QUINA PRIL HYDRO CHLOR IDE USP
Format No.: QA/FM-235/00
A.R. No. : FG/0483/17 Date of Exp. : JUN-2022
Sr.# TESTS RESULT S SPECIFI CATION
I. Descriptio n White powder A wh ite to off-white powder, with pink cast at
times.
3. Identifica tion The [nfrared spectrum of test sa mpl e shou ld be
Complies concorda nt with simil ar preparatio n of that of
a) By JR Spectrum Quinapril Hydrochl oride WS/ RS.
b) By HPLC Complies T he retention time of the major peak in the
chromato gram of assay preparatio n should be
correspon d to the clu·omato grarn of the standard
preparatio n, as obtained in the assay.
4. Specific Optical Rotation + 14.97° Between+ l4.4° and + 15.4° at 25 °C on
anhydrou s basis.
5. Water Content (By KF) 0.83 % w/w Not more than 1.0% w/w
6. Residue on Ignition 0.06 % w/w Not more than 0.1 % w/w
7. Content of Ch lorid e 7.36 % Not less than 7.2% and Not more than 7.6%
(By potentiom etry )
8. Re lated Compoun d 0. 19 % Related Co mpound A :NMT-0.5 %
(By HPLC) 0.05 % Re lated Co mpound B :NMT-0.5 %
0.08 % Any unknown impurity :NMT-0.1 0%
0.39% Tota l impuriti es :NMT-2.0 %
9. Assay 99.02 % Not less than 98 .5% and Not more th an IO 1. 5%
(By HPLC) on anhydrou s bas is.
10 . Residu a l so lvent Not Detected Acetone N MT 2000 ppm
(By HSG C) 2 1 ppm Acetonitril e NMT 4 10 ppm
Not Detected Di-isopro pyl ether NMT 700 ppm
68 ppm Ethyl Acetate NMT 3000 ppm
Not Detected Toluene NMT 890 ppm
Addition al Test
1. [ Pa lladium Content 3 ppm [ Not more than 0.001%(1 0 ppm)
Remark: The material complies as per USP and above specificati on.
Pre ared B
Manage r
Quality s_s_u_r_a_n_c.,,..
e Quality Contr
Note: Methyl ene chloride is not used in the manufact uring process.
Precaut ion: Do the handling of materi a l under nitrogen gas because it is hi ghl y hygrosco pic in nature.
Storage: Store at temperatu re between 2 - 8 ° C
HEAD OFFICE :
71, Udyog Kshetra, 2nd Floor, Mulund Goregaon Link Road, Mulund (YV), Mumba
i - 400 080. INDIA
Tel.: 00 - 91 - 22 - 67976666, 67976697, 25918195 •Fax: 00 - 91 - 22 - 259048
06, 25653185 / 3234
Regd. Office:
January, 2020 Plot No. 801/23, G.I.D.C.
3.2.S.4.4 BATCH
Estate, Phase ANALYSIS Page 3
- III, Vapi-396195, Dist- Valsad, Gujarat, INDIA.
Website : www.aarti-industries.com • CIN: L24110GJ1984PLC007301
Factory: Unit - IV, Plot No. E-50, MIDC, Tarapur,
Taluka & District- Palghar, Pin - 401506. Maharashtra, INDIA.
Tel.: +91 8983035452, 8983065452, Telefax: (02525) 661092
Format No. : QA/FM-235/00
Batch No. : QN-17023 Date of Mfg. : AUG-2017
A.R. No. : FG/0484/17 Date of Exp. : JUL-2022

I. Description White powder A white to off-white powder, with pink cast at
tim es.
2. Solubility Compl ies Free ly So lubl e in water.
3. Identificat ion The Infrared spectrum of test sa mpl e shou ld be
Com plies concordant with s imilar preparation of th at of
a) By IR Spectrum Quinapril Hydrochloride WS/RS.
b) By HPLC Complies The retention time of the major peak in th e

correspond to the chromatogram of the standa rd
preparation , as obtained in the assay.
4. Specific Optical Rotation + 14.96° Between+ l4 .4° and + 15.4° at 25 °C on
anhydrous basis.
5. Water Content (By KF) 0.86 % w/w Not more than 1.0% w/w
6. Residue on Ignition 0.05 % w/w Not more than 0.1% w/w
7. Content of Chloride 7.39 % Not less than 7.2% and Not more than 7.6%
(By potentiometry )
8. Re lated Compound 0. 13 % Related Compound A :NMT-0.5%
(By HPLC) 0.03 % Related Compound B :NMT-0 .5%
0.06 % Any unknown impurity :NMT-0.10%
0.27 % Total impuriti es :NMT-2.0%
9. Assay 99.34 % Not less than 98.5% and Not more than IO 1.5%
(By HPLC) on anhydrous basis.
I 0. Residual so lvents Not Detected Acetone NMT 2000 ppm
(By HSGC) 17 ppm Aceton itril e NMT 410 ppm
Not Detected Di- isopropyl ether NMT 700 ppm
l 787 ppm Ethy l Acetate NMT 3000 ppm
Not Detected To lu ene NMT 890 ppm
Additional Test
I. I Palladium Content 4 ppm I Not more than 0.001% (10 ppm )
Remark: The material comp li es as per USP and above spec ification .
Pre
~Designee Manager Head

QualiiyAssurance Quality Assurance Quality Cont
Note: Methy lene chloride is not used in the manufacturing process.
Precaution: Do the handling of material under nitrogen gas because it is hi ghl y hygroscop ic in nature.
Storage: Store at temperature between 2 - 8 ° C
HEAD OFFICE :
71, Udyog Kshetra, 2nd Floor, Mulund Goregaon Link Road, Mulund (YV), Mumbai - 400 080. INDIA
Tel.: 00 - 91 - 22 - 67976666, 67976697, 25918195 •Fax: 00 - 91 - 22 - 25904806, 25653185 / 3234
January, 2020 Plot No. 801/23, G.I.D.C.
Regd. Office: 3.2.S.4.4 BATCH
Estate, PhaseANALYSIS Page 4
- III, Vapi-396195, Dist- Valsad, Gujarat, INDIA.
Website : www.aarti-industries.com • GIN: L24110GJ1984PLC007301
OPEN PART

3.2.S.4.5 JUSTIFICATION OF SPECIFICATION
Specifications and test procedures as described in the monograph of Quinapril

Hydrochloride USP have been adopted for testing Quinapril Hydrochloride for
compliance.
For residual solvents internal limits for the specifications for residual solvents
have been fixed according to those specified in ICH guidelines -Q3C (R3) dated
November 2005, wherever applicable.
Since IPA is not used in the manufacturing process, it could be present in the
starting material, it is not detected i.e. below detection limit, it is a class 3 solvent,
and hence it has been excluded from the specifications of the final product.
For related substance test, in-house method has been developed and suitably
validated.
As per USP, Related compound A, Related compound B is limited to 0.5%, N-
acetyl quinapril at is limited 0.15%, single unknown impurity is limited to NMT
0.10% and Total impurities are limited to NMT 2.0%.
For assay, USP 32 HPLC method has been developed and suitably validated.
Method for Chiral purity of S-I-compound has been developed and suitably
validated and R-isomer is limited to NMT 0.20%.
January, 2020 3.2.S.4.5 JUSTIFICATION OF SPECIFICATION Page 1

OPEN PART

3.2.S.5 REFERENCE STANDARDS OR MATERIALS
Quinapril hydrochloride working standard FG/WS/0027/16 was standardized

against Quinapril Hydrochloride reference standard.
Listed below the list of reference standard used for analysis:
Standard Batch no / Lot no

Quinapril Hydrochloride RS HOL434
Quinapril Related compound A FOC 114
Quinapril Related compound B FOC 116
Residual Solvents:
For residual solvents AR / HPLC grade solvents have been considered as
reference standards.
The certificate of analysis of batch no FG/WS/0027/16 has been included on

following pages.
January, 2020 3.2.S.5 REFERENCE STANDARDS OR MATERIALS Page 1

OPEN PART

3.2.S.6 CONTAINER CLOSURE SYSTEM
Quinapril Hydrochloride is packed in antistatic polyethylene bags under nitrogen.

These bags are twist tied and fastened using a nylon fastener. These bags are
placed in triple laminated sun barrier (TLSB) bags/ pouches. The TLSB
bags/pouches are heat-sealed. All bags/pouches are labelled with the product
label and placed in EPS box (EPS – Expanded Polystyrene Box) which is lined
with cooling cube (which contains monoethylene glycol sealed in food grade
HMHDPE Cube) to maintain controlled room temperature during transit. The
EPS box is closed, sealed using BOPP tape and transferred to 5 ply / 7 ply
corrugated box. This box is sealed using BOPP tape, labelled and dispatched.
January, 2020 3.2.S.6 CONTAINER CLOSURE SYSTEM Page 1

OPEN PART

3.2.S.6.1 PACKING MATERIAL SPECIFICATIONS & TEST PROCEDURES
Following table gives the details of the packing materials used for the packing of
Quinapril HCl.
S.N. Description of Material Specification
1 65 Liter HDPE Drum AQC/SP/PM/19

2 Triple laminated sun barrier bags AQC/SP/PM/02
3 EPS Box AQC/SP/PM/31
4 Antistatic Black polythene bags AQC/SP/PM/09
5 Antistatic Natural polythene bags AQC/SP/PM/10
Packing material Specifications are given in following page no. 2 to 14.
Antistatic polythene bags comply with European directive regulation (EU) No.
10/2011 as amended and it also complies with FDA regulation CFR title 21,
177.1520, olefin polymer.
Food grade certificate for antistatic polyethylene bags is provided after the
specifications and test procedure for antistatic natural polythene bags (on Page
no. 15)
January, 2020 3.2.S.6.1 PACKING MATERIAL SPECIFICATIONS Page 1

AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
AND TEST PROCEDURES
Tel.: 02525 273029
COMFORT ROBBER IHDOSTRIES

Mfg. of : H.O.P.E. I P.P. Woven Bags, Polythene Sheet, Rolls & Bags.
Factory : Plot No. W- 26, M. I. D. C. Tarapur, Boisar, Dist. Palghar- 401 506, Maharashtra, India.
e..mail : ssshekhawat1 @gmail.com
DATE:- 27.1Cf.16
To,
M/s. 1\arti Industries Ltd
E-50, MIL)C, Tarapur.
TO WHOMSOEVER IT MAY CONCERN

This is to certify that we have been supplying Polyethylene Bags to M/s. !\ani
Industries Ltd. (Natural Polyethylene Bags) ·rhe granuals (Ciradc 24~:S040) u
for n1anufacture or Polyethylene Bags is of 1nake M/s. Reliance industries l.td.
This Grade of C:iranuals (C}rade 24FS040) ITI.eets the requireinents or Indian

Standard IS-1 0146-2003 on "'Polyethylene for its safe usc in contact vvith rood
sturfs, pharn1aceuticals and drinking water.'' I_t also conrornls to the positiVL' list or
constituents as approved in IS: I 0 141 :2003. The grade con1 pi ics \\ i th I: Di\
regulation: CFR title 21, 177.1520, ()le fin poly1ner.
The grade also cornplieswith the require1nent of 1nonograph 3.1.3 on Polyolclins.

The grade also COlnplies with r:uropcan directive regulation (LlJ) ~0. ]()."'Oil~~~
an1cndcd.
Thanking You,
Your's Faithfully,
For:- Comfort Rubber Industries
3
(Authorized sign)

AND TEST PROCEDURES
OPEN PART

3.2.S.7 STABILITY
January, 2020 3.2.S.7 STABILITY Page 1

OPEN PART

3.2.S.7.1 STABILITY SUMMARY AND CONCLUSION
3.2.S.7.1.1 GENERAL
Quinapril Hydrochloride is under stability since October 2005.

Following the review of the process, it was observed that n-pentane is a fire
hazard and was posing handling problems in the plant. Hence it was decided to
replace n-pentane (for making slurry of Quinapril hydrochloride and washing the
centrifuge cake) with a more acceptable solvent like ethyl acetate which is also a
class 3 solvent. In addition it helped in omitting a solvent. This change was
effected from September 2006.
3.2.S.7.1.2 STRESS TESTING

The stress studies on Quinapril Hydrochloride B. No. AH/0410/286 was carried
out as the following conditions:
Sr. No. Stress Condition Stress sample
1 1 M HCl 100 mg + 10 ml diluent + 5 ml 1 M HCl
2 1 M NaOH 100 mg + 10 ml diluent + 5 ml 1 M NaOH
3 50 % H2O2 100 mg + 10 ml diluent + 5 ml 50 % H2O2
4 100 mg + 10 ml diluent + 5 ml of water Heat
Heat and water
80° C 1 hr.
5 UV Exposure 100 mg exposed to UV light.
6 Light exposure 100 mg exposed to light and atmosphere.
7 Heat (105C) 100 mg exposed at 105C for 3 hrs
8 35 % HCl 100 mg + 10 ml diluent + 5 ml 35% HCl
9 0.1 M NaOH 100 mg + 10 ml diluent + 5 ml 0.1 M NaOH
10 Sunlight exposure 100 mg exposed to sunlight for 3 hrs.
The HPLC method for related substances as given in the United States
Pharmacopoeia was adopted to check its suitability as a stability indicating
method.
January, 2020 3.2.S.7.1 STABILITY SUMMARY AND CONCLUSIONS Page 1

OPEN PART

%Area of known and unknown impurities formed during degradation studies are
tabulated – refer to the following Table:
RRT of Impurities
Stress
Condition Main Peak Related B 1.92-1.94
0.93 1.03 1.36 2.71
1.0 0.50-0.53 Related A
Untreated 99.43 0.49 -- -- -- 0.03
1 M HCl 98.21 0.60 --- --- --- 1.12 ---
1 M NaOH --- 94.14 3.05 2.57 --- 0.07 ---
50 % H2O2 96.35 0.46 --- --- 0.45 2.13 0.28
Heat and
75.53 0.35 --- --- --- 24.05 ---
water
UV Exposure 95.88 0.49 --- --- --- 3.52 ---
Light
96.59 0.49 --- --- --- 2.88 ---
exposure
Heat (105C) 96.15 0.49 --- --- --- 3.29 ---
35 % HCl 98.13 0.79 --- --- 0.96 ---

0.1 M NaOH 98.05 0.51 --- --- --- 1.38 ---
Sunlight
95.62 0.48 --- --- --- 3.84 ---
exposure
The results indicate that there was significant degradation under strong alkaline
conditions (1M NaOH) wherein the Quinapril got almost fully converted to
Impurity B and few other degradation products. When exposed to heat and
humidity the major degradation product observed was Impurity A. Slight
degradation was observed under all other conditions viz – acidic conditions,
exposure to sunlight, oxidation, UV light etc.

OPEN PART

SUMMARY
From the results it could be concluded that:
1. The HPLC method for related substances as per USP is able to detect
degradation products and hence could be used as a stability indicating
method.
2. Quinapril is sensitive to heat and humidity hence needs a packing to protect

from excessive heat and moisture.
3. Quinapril is also susceptible to strong alkaline conditions.
CONCLUSIONS
From the results it could be concluded that the method for related substance is
able to detect known and unknown impurities and hence could be used as a
stability indicating method.
The forced degradation studies chromatograms are appended on following page

no 4 to 177.

OPEN PART

3.2.S.7.1.3 SELECTION OF BATCHES
Three consecutive validation batches, after the process change in September
2006, as per the details given below were selected for the stability studies.
Sr.No. Batch No. Mfg. Date

1. QN-06001 OCT 2006
2. QN-06002 OCT 2006
3. QN-06003 OCT 2006
The batch size was increased from 75 kg to 150 kg input of Benzyl Quinapril
Maleate and the process was validated. Three consecutive validation batches have
been kept for stability study as given below.

1. QN- 11001 MAY 2011
2. QN- 11002 MAY 2011
3. QN- 11003 JUN 2011
Three consecutive validation batches, after the process change in March 2013, as
per the details given below were selected for the stability studies.

1. QN-13005 MAR 2013
2. QN-13006 APR 2013
3. QN-13007 APR 2013
Current process validation batches as per the details given below are included in
stability studies.
Sr. No. Batch No. Mfg. Date

1. QN-16033 JUL-2016
2. QN-16034 JUL-2016
3. QN-16035 AUG-2016
Following annual batches were included in the long term stability studies.
1. QN-14001 JAN-2014
2. QN-15001 MAR-2015
3. QN-16001 JAN-2016
4. QN-17001 JAN-2017
Subsequently one batch every year will be included in the long term stability
studies.

OPEN PART

3.2.S.7.1.4 CONTAINER CLOSURE SYSTEM
The stability samples are packed in the antistatic polythene bags and TSLB bags.
They are placed in EPS boxes to simulate market conditions.
3.2.S.7.1.5 SPECIFICATIONS
The stability study specification and test procedure used for analysis of stability
samples of drug substance Quinapril Hydrochloride is provided on following
page no 180 to 187.
3.2.S.7.1.6 TESTING FREQUENCY
The following Table gives the frequency of testing of stability samples.

Study Duration
Accelerated stability studies 6 months
Long term stability studies 5 years
3.2.S.7.1.7 STORAGE CONDITIONS

The storage conditions are given below:
Study Storage Conditions
Accelerated stability studies 25C  2C / 60% RH  5%
Long term stability studies 5C  3C

,
• Aarti Industries Limited

Unit-IV, MIDC, Tarapur
Quality Control
MASTER COPY
Aarti Industries LtcL
Unit IV
Stability Study Specification

Finished Product Name: uina ril h drochloride Pa e No.: 1/1
S ecification No.: Effective Date: Su ersedes: Revision No.:
A C/SP/SB/OOI 04/11/10 New 00
Material Code: STP No.: AQC/ST/SB/OOI
Reason for chan e:CC No.: C/1O-042
Prepared By Checked B Authorized By
~.).~ l'\\O
Executive - Q~ft';; Control
a":l 1It16
Head - Qu ity Control
~~".o
\;Head - Quality Assurance
Reference: USP - 32/NF-27 and In-house
Sr. Tests Specification

No.
1 Description A white to off-white powder, with pink cast at times.
2 Specific Optical Between +14.4° and +15.4° at 25°C on anhydrous basis.

Rotation .
3 Water Content Not more than 1.0% w/w

··(ByK.F)
4 Related Related Compound A :NMT-0.5%
Compounds Related Compound B :NMT-0.5%
N -acetyl quinaprilate :NMT-0.15%
Any unknown impurity :NMT-O.lO%
Total impurities :NMT-2.0%
5 Assay Between 98.5% to 101.5% on the anhydrous basis.
(By HPLC)

MASTER COpy
Anti Industries
Unit IV
Ltd.
Finished Product Name: P e No.: 1/7

STPNo.: Revision No.:
AQC/ST/SB/OOI 00
Material Code:
Reason for chan e:CC No.: C/l0-042
Prepared By C~ Authorized By
Y1\~~\\l. ~. ~~ltv
Executive - uali Control Head - uali Control \liead - uali Assurance
Sr. Tests
No.
1 Description
A white to off-white
powder, with pink cast
at times.
2 Specific Optical Reagents required for analysis

Rotation (SOR) Reagent Name
Between + 14.4° and 1) Methanol A.R. grade
+15.4° at 25°C on Sample preparation:
anhydrous basis. Weigh accurately 0.500 g of sample in a 25 ml of volumetric
flask, dissolve in & dilute up to the mark with methanol, adjust
the temperature of diluent and sample solution at 25°C. Select
wavelength of the D line of sodium (A.) 589 nm. Perform blank
determination with diluent for necessary correction (auto zero)
and sample determination at 25°C (±O.5°C).
a x 25
SOR (On as is basis) = ----------------------------------
WxL
SOR (On as is basis) x 100

SOR (On anhydrous basis) = -------------------------------
100-WC
Where,
a. : Optical rotation of sample solution.
L : Length of polarimeter tube in decimeter.
W : Weight of sample in g.
WC : Water content in %
Water Content Procedure:
(ByKF) Fill the methanol into the titration vessel till the electrode tip
Not more than 1.0%w/w dip in it and titrate with KF reagent, which is standardized
earlier, to neutralize the methanol. Weigh accurately 0.500g of
sample & transfer into the titration vessel. Titrate with the KF
reagent to electrometric end point &. calculate the % of water
by using formula,

t_· ••..
_-·_ •.
---·""'~,
•.•.
v·•.•.•.•
··,.••
_-, ~~_·~·~··---l
•••.-" ,.,' ••..•.•
U·I~·C<.1:,I~'j~It()i.4,.. \
_<41

MASTER COpy
Aarti Industries LtcL
Finished Product Name: P eNo.: 2/7

STPNo.: Revision No.:
A IST/SB/OOI 00
Material Code:
Reason for chan e:CC No.:
Prepared
Sr.
No.
vxFx 100
Water (% w/w) = ----------
W x 1000
Where,
V = Volwne of KF reagent conswned in MI
F = Water equivalence factor ofKF Reagent in mg/mL
W = WeiJ!ht of sample taken in g
Reagents required for analysis
Reagent Name
Related Compound A 1) Monobasic ammoniwn phosphate
NMT-o.S% 2) Phosphoric acid
3) Acetonitrile HPLC grade
Related Compound B 4) Methane sulfonic acid A.R. grade
NMT-O.S% 5)Reference solution No. of System suitability Solution in
~ Related comPounds (By HPLC) Test ~'
N -acetyl quinaprilate 6)Reference solution No. of standard Solution in
:NMT-0.1S% Related compounds (By HPLC) Test
Mobile phase preparation:
Any unknown impurity 0.025 M, Monobasic ammonium phosphate solution:
:NMT-o.IO% Weigh accurately 1.720g monobasic ammoniwn phosphate
(NH.H2P04), transfer into 1000 ml of beaker, add 600 ml of
Total impurities NMT- water, dissolve it and adjust the pH 6.5 with phosphoric acid.
2.0% Mobile phase:
Take 720 ml HPLC water, 280 m1 of Acetonitrile HPLC grade
and 1 ml of Methane sulfonic acid in a 1000 ml of HPLC
bottle, mix well and sonicate for 5 min. Filter the mobile phase
with 0.45Jl nylon membrane filter and degas.
Diluent:
Take 600 ml of 0.025 M, Monobasic ammoniwn phosphate
solution in 1000 ml of beaker, add 400 ml of Acetonitrile
HPLC grade and sonicate for 5 min. Filter the diluent with
0.45Jl nylon membrane filter and degas .
J!.'1te: The total volume ojmobi/e phase shall be decided on the
basis of number of samples.

~-"",~--,.""-~ .•.
,,,- ••""'",-,;,,-~-.,-,, •.,,.•.,; ~-";.:<_ •.""~
UI~C (J~.~>~
r.fR {-jl }.~...;;.... ~i.i I "i
....--.Jo
•
,
Aarti· Industries Limited MASTER COpy
Unit-IV, MIDC, Tarapur Aarti Industries Ltd.
Tt_aro
Finished Product Name: Pa eNo.: 3/7

STP No.: Revision No.:
A C/ST/SB/OOI 00
Material Code:
Prepared By ~
\to
lb·"Ih..~~ O,1ll 0'3' !t1\6
Executive - ual ControlHead - ~i Control
Sr. Tests Test procedure

No.
Solution preparation:
Standard Stock Solution-I:
Weigh accurately 0.005g of Quinapril Related compound A &
0.005g of Quinapril Related compound B transfer into 10 ml of
volumetric flask, dissolve in & dilute up to the mark with
diluent, and mix well.
Standard Stock Solution-2:
Weigh accurately 0.006g ofN -acetyl quinaprilate in 100 ml of
volumetric flask, dissolve & dilute up to the mark with diluent,
and mix well.
System suitability Solution:
Weigh accurately O.IOOgof Quinapril HCL WS & transfer into
50 ml of volumetric flask. Add 0.5 ml of standard stock
solution -I dissolve & dilute up to the mark with diluent.
Note : System suitability solution shall ,be used as long as the
~ elution pattern matches with that of chrpmatogram as shown in
annexure-/
Standard Solution:
Pipette out 1 ml of standard stock solution-I and 5 ml of
standard stock solution-II into 100 ml of volumetric flask,
dilute up to the mark with diluent, and mix well.
Test Solution:
Weigh accurately 0.100g of sample, transfer into 50 ml of
volumetric flask, dissolve in and dilute up to the mark with
diluent, and Mix well.
Instrument Details :
i) Agilent Technologies 1200 series uv/visible detector
ii) Waters Alliance 2489 uv/visible detector
Hi) Waters Alliance 2996 PDA detector
Chromatographic conditions:
Column : 250mm x 4.6 mm x5J.1m,packed with
Nitrile group chemically bonded to
porous silica particles
( Nucleodur 100-5 CN -RP suitable)

Quality Control
Aarti Industries Ltd.
Unit IV
Stabili Stud Standard Test Procedure

Finished Product Name: ril h drochloride P e No.: 4/7
STPNo.: Effective Date: Su ersedes: Revision No.:
AQC/ST/SB/OOI 04/11/10 New 00
Material Code:
Prepared By Authorized By
~~0\"1~
Executive - ~~ 1ontrol Head -
L..
'
~ead
~~'tO
- uali Assurance
Sr.
No.
Detector : V.VI PDA. Detector
Wavelength : 214nm
Injection volume : 10Jll
FlolV rate : 1.5 mIl minute
Run time : 50 minutes
Procedure:
Saturate the HPLC column with mobile phase for 35 minutes.
Check the baseline. Inject trial run and make adjustment if
necessary and inject the sample as per following sequence.
1) Inject 10Jll diluent as blank in duplicate,
2) Inject 10Jll system suitability solution in singlet,
3) Inject 10Jll diluent as blank in singlet
4) Inject 10Jll of standard solution in six replicate,
5) Inject 10Jll test solution in duplicate,
6) Inject 10Jll system suitability in singlet as bracketing
standard in singlet !
If analysis of sample more than one at a time then inject

bracketing
standard system suitability in singlet after each six replicate
injection.
System suitability solution :
A) System suitability:
i) The resolution between the peak due to Quinapril and
Quinapril related compound A should not be less than 1.75
ii) The resolution between the peak due to Quinapril and
Quinapril related compound B should not be less than 3.5
iii) The column efficiency should not be less than 550
theatrical plates.
B) standard solution:
i) The % RSD of six replicate injection of standard solution
should not be more than 2.0%.
C) System suitability: (Bracketing standard)

Unit-IV, MIDC, Tarapur Aarti Inclustriss Ltd.
UnitlV
Finished Product Name: P eNo.: 5/7

STP No.: Revision No.:
AQC/ST/SB/OO 1 00
Material Code:
Reason for chaD e:CC No.: C/I0-042
Prepared By ~
AJfh....•J<v~~ pf>
'\ o,..{ I ' if1 \,,\ 0
Executive - ua1 Control Head - ~i Control
Sr.
No.
Quinapril related ·compound B should not be less than 3.5
ni) The column efficiency should not be less than 550
theatrical plates.
If the system is not suitable make adjustment and repeat the analysis.
Calculation:
1) Calculate the percentage of each Quinapril related
compound in the portion of Quinapril Hydrochloride taken by
the formula:
ART Ws
% Of Impurities = --------- x -------- x 100
ARS WT
Where,
ART : Average area of respective impurity in test solution.
AR S : Average area of respective impurity in standard solution
WRS : Weight of respective standard solution in/g
WT : Weight of in test solution in g
2) Calculate the each impurity in Quinapril Hydrochloride by
area normalization method
Assay Reagents required for analysis

(By HPLC) Reagent Name
Not less than 98.5% and 1) Quinapril hydrochloride WS
Not more than 101.5% Mobile Phase preparation : Refer Related compounds
on anhydrous basis. (By HPLC ) Test No.4
Diluent : Refer Related compounds
(By HPLC ) Test No.4
Solution preparation:
System suitability solution: : Refer Related compounds
(By HPLC ) Test No.4
Standard solution:
Weigh accurately 0.100g of Quinapril hydrochloride WS and
transfer it into 50 ml of volumetric flask, dissolve and dilute up
to the volume with diluent. Mix well.

~-"-'--"'J
UNCOI~l~{'OLLED .
• AartiIndustriesLbnffed
MASTER COpy
Aarti IndlsEottriE: '.~d..
Pa e No.: 6/7
Su ersedes: Revision No.:
New 00
Sr.
No.
Test solution:
Weigh accurately 0.100g of sample and transfer it into 50 ml of
volumetric flask, dissolve and dilute up to volume with diluent
. Mix well
Chromatographic conditions:
Refer Related compounds (By HPLC) Test No.4
Except run time
Run time : 30 minutes
Procedure:
Saturate the HPLC column with mobile phase for 30minutes.
Check the baseline. Inject trial run and make adjustment if
necessary. And inject the sample as per following sequence,
1. Inject 10J.lIdiluent as blank in duplicate,
2 Inject 10J.lIsystem suitability solution in singlet,
2. Inject 19J.lIstandard solution in six replicate,
3. Inject WJ.lItest solution in duplicate,~
4. Inject 10J.lIdiluent as blank in singlet,
5. Inject 10J.lI standard solution in duplicate as bracketing
standard
If analysis of sample more than one at a time then inject
bracketing standard in duplicate after each six replicate
injection.
Calculate the percentage of Assay by using the mean area of
six replicate injection of standard solution.
System suitability solution :
A) System suitability:
Quinapril related compound B should not be less than 3.5
Hi) The column efficiency should not be less than 550
theatrical plates.
B) standard solution:
i) The % RSD of six replicate injection of standard solution
.,.< s~C?W~potbe ipore tb~ 2.0%.

~

Quality Control
MASTER COpy
Aarti InaG3tli66 Ltd.
Unit IV
Stabili Stud Standard Test Procedure

Finished Product Name: Quina ril h drochloride Pa e No.: 7/7
STP No.: Effective Date: Revision No.:
A C/ST/SB/OOI 04/11/10 00
Material Code:
Prepared By Checked By
fth\~AJ~\W ~,
Executive :. ~~ft
Control Head - all Control
Sr. Tests Test procedure

No.
ii) The % RSD of four replicate injection of standard solution
(Standard injection 5th, 6th and bracketing standard I st and 2nd)
should not be more than 2.0%.
If the system is not suitable make adjustment and repeat the
analysis.
Calculation:
AT Ws
x ________ P
x _____________
Assay = -------- x 100
As WT (IOO-WC)
Where,
AT :Average area of test solution.
As :Average area of standard solution.
Ws :Weight of standard solution in g.
WT :Weight of test solution in g.
P : Percentage of purity of working standard on as is
~
,
0;.,
basis 0
'
WC : Water content in%

OPEN PART

3.2.S.7.1.8 EVALUATION
1. Quinapril Hydrochloride was stable at accelerated stability conditions - 40C
 2C / 75% RH  5% up to four months. After four months it was found to
be unstable as samples showed level of impurity À` is exceeding specified
limit (0.5%).
2. Quinapril Hydrochloride was found to be stable at intermediate stability

conditions - 30C  2C / 65% RH  5%. But the level of Impurity À` is
gradually increasing within six months.
3. Quinapril Hydrochloride was found to be stable at long term stability

conditions - 25C  2C / 60% RH  5%.
4. Quinapril Hydrochloride was found to be stable at long term stability

conditions - 5C  3C. As a precautionary measure the samples were kept at
5C  3C. seeing the trend at Intermediate conditions, the testing of samples
kept at 5C  3C was initiated from 6 months onwards.
Accelerated stability studies at 40C  2C / 75% RH  5% have been
discontinued and long term stability study at 25C  2C / 60% RH  5% &
5C  3C are continuing.
In view of above stability conditions at 25°C  2°C/60% RH  5% have been

considered as Accelerated stability conditions. And the Stability conditions
at 5°C  3°C as long term stability conditions.
3.2.S.7.1.9 STATEMENT/LABELING
STORAGE CONDITIONS
Preserve in well closed containers and store at temperature between 2-8°C.
RETEST PERIOD Five years

OPEN PART

3.2.S.7.2 POST APPROVAL STABILITY STUDY PROTOCOL AND
COMMITMENT
STABILITY PROTOCOL
Study Storage Conditions Duration
Long Term Stability Studies 5C  3C 5 years
Number of batches One batch after every one year.
Packing of stability samples The stability samples will be packed in the
antistatic polythene bags and TSLB bags.
They will be placed in a EPS box to
simulate market conditions
Testing Frequency
Five years Initial, 3, 6, 9, 12, 18, 24, 36, 48 & 60
months
The test conditions as specified above will be followed.

The specifications and test procedures as given in Section 3.2.S.7.1.5 will be
followed.
The stability protocol is given on following pages.
COMMITMENT
The stability studies will be undertaken as per the above mentioned protocol
and the results of the stability studies will be maintained and any adverse
stability test results will be communicated to authority.
January, 2020 3.2.S.7.2 POST APPROVAL STABILITY STUDY Page 1

PROTOCOL AND COMMITMENT
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SU~/tJ\.1./\.R Y REPORT: INTER!v1EDJA TE
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2.0 ST ABILlT\' STUDY P'ROCEDtiRE
2.1 PTJRPOSE:
This protocol 1s created in accordance Vl'ith the ICH stability guidelines to generate
accelerated stability, intermediate stability and Long--term stability studies for QUJNAPRlt
ll'r'DR (){' f1t.ORIDE.
2.1 SCOPE:
This protocol is applicable to QUlNAPRlL HYDROCHLORIDE. presentations, requiring
::v~celerated stability, Intermediate stability and Long term stability studies at Aarti Industries
Limited, Tarapur.
!..._~. LOC'.~.T!O!'!:
Qua !ity Conlrol Department.
2.4 RES"PONSlBILITIES:
Qua!ity ft...ssurance Department:
Preparation of the stability study piolocol.
/-..pproval of the stability study protocol.
Quality Control Departn1ent:

T (}carry out the stability study as per the schedule .
.Revie'N of protocol, and certification of Accelerated stability. lnte1mediate stability and Long
tc:rrn stability· studies for QUINAPRIL HYDROCHLORIDE after revievv'ing filled report.
2.5 lVIATERlAL, :EQ'UIPMENTS:
2.5.1 Material:
Stability samples ofQUINAPRIL HYDROCHLORIDE. (API).
(A fler a finished product is manufactured & released, samples are co! lee ted as per finished
product sampling procedure.)
2.5 .2 Equipmcnts and Storage conditions:
5.2.1 Stability Chamber (Make: Thermolab)
5.2.2 Storage conditions:
,.L\cceferated stability study: Temperature: 25°C t 2 cc
Humidity: 60 ~/f,RH :t 5 0./0RH
Long-term stability study: Temperature: Y:;C ± 3 8

(

·.;-·-~..,..,.,.-..-,..,~-.---~-=----·--·_,..,.....,..,._~-·-~-------~-, r.....,....,., ....~ ....,.,...,.,..,;,..;-:,oo.,~-'-'--'"""''~T""'"'"'J:·r......,r.:.,..!Or"'.--.., ... ~_....,.....,.,~..,..•..-- ..-.-.....-.••--~..,--,.~'i
~ Aarti Industries Limited ·

f Unit-IV; lVliDC, Tarapur i
~ .. ·~-
- (APl-i\~.anufacturin~ Un1~
_ -=-~~===,r==-~====··=~=·-~-----~-"----~
Iw- -- . - ······-:_----
StabilitY
.. - - .
----~-----···-·--.-~------
Study Protocol
---~-- - - - - - -.. ----- -- --------------------- ---····-- --- --- -- -- __
-·--:----·-~-- ----~----"----.:.--·
l Page No: S uf 6 ~ l ________________________ ------~----- ····-. --------. -- ~
l Product-Name: QUINAPRIL H'\'DHOCIILORIDE ~

t--------:---·-- ----------------· ------- -----------~----·--------· -------------------- -- ···-· ---,- --------------······· ·-------·· .... 'll
~----------Prot~_£Q~-~-o.: __ ~f!~ctive Date: L________
L~~~!·se_des _:__j ____ Re,:·isio_!~}~:.:_ --~
L~.~-~SB(P~~}N.:OOI j Ol/01/08 ~~~~..--1~- NiA I ____..2.2_~~~--J
2.6 SELECTIC)N OF BATCHES:
Norm~:dly three production batches preferably validation batches shall be placed on the
stability monitoring program and thereafter one comrnercia!: batch per year of the APl
manufactured.
2.7 STA.BILlTY STUYDY DURATION:

2.7. i Stability study duration
The foii'owing table gives the duration of testing-of stabiiHy samples.
:--.-----·-·····---·------~--------··--··--r---. ··---··---:-·-----------------------·1
l--~--- ·------· · ·-·----:-·--·· .~tu_af
. ------+--·________1!_~!~.!~~!!.- --. ---- -------- ---1
~-~:·_ce_l~!~ted ~ta~~hty stud~, I --~-~:2~_ths_________________ ----~
1 Lon~-~er~-_:_~~b1hty study 1 60 m~~~1tl~s ___ ______ _]
.., ry .,
_,lfJ· I ..-.:..t Testing frequency:
The following table gives the Testing frequerrcy of stability samples. _ _____ _ _ _
r--c~;;~~I~_:,;-r!Mf 2M 1=1~141\1 IsM f6Iil9M r~i:.L_---l~~[~~-~~=IJ.6!\1 1_ 48!'x~r~~Q~~f::_:
! Acrden.1-tt>d J ! i l ; ! ~ ! ; i i i .
t stabiiiry I .;/ I ../ ! ../ i l .x i I l< l ~ ;
+
i / I X ( ../ x i x x i x
~-·i_~~~i={;·~~:;~--i--=-t----+----t---t-·t----f--~----·-~------l---·---- -----·----t-----------+-~--------·i··. ~ -.....

l 'T I I
I
! s ant tty
I
~ x 1 X
I
! -v' ' .X l .)(.
I
l -v' I ../
' ;
! ../
'
i ./
:
: ./
'
; /
I
t ../
I
~ v-··
! st_l!~L ______L_~__j_. I . : i '~---·-L ___l________l ______________.L______l _________l ______ _
·/: To be done x: Not applicable
2.8
CONTAIN:ER CLOSURE SYSTEM:
QUINA PRlL HYDROCHLORIDE. is packed in double polyt:th::l:?:1e bags i e. outer bbck
antistRtir· ::'1°!),-':"thylene and inner natural antistatic polyethylene bags under nitrogen. These
bags are placed in triple laminated sun barrier (TLSB) bags. The_'/ are placed in EPS boxes
\vhich is to simulate market conditions.
2.9
SAivlPLE QUAl"~TITY:
Sarnpk to be kept for stability study in such way that each sample quantity is sufficient for
duplicate anaiysis as per stability specification and ;_-...,,u exir;:J sample quaniity of each sto;·agc
condition is kept for reanalysis or any spillage during stab!l.ity study.
The sa1nple quantity required for,
Accelerated stability study : 5 x 3.0 g + 2 x 3.0 g ::-= 7 J g
Long term stability study : 9 x 3.0 g + 2 x 3.0 g == 33 g
Total sample quantity : 54 g

2.10 DOCL11\,1ENTS REQLflRED
2.1 OJ Analy1i,'al report and· analytical protocol:

Eefer anached _-\NNEXURE-J
2.10.~ Sumnun~y report:

.Re1er ~JlLiched ANNEXURE-II

OPEN PART

3.2.S.7.3 STABILITY DATA
Three consecutive validation batches, after the process change in September
2006, as per the details given below were selected for the stability studies.
1. QN-06001 Oct 2006
2. QN-06002 Oct 2006
3. QN-06003 Oct 2006
The batch size was increased from 75 kg to 150 kg input of Benzyl Quinapril
Maleate and the process was validated. Three consecutive validation batches have
been kept for stability study as given below.

1. QN- 11001 May 2011
2. QN- 11002 May 2011
3. QN- 11003 Jun 2011
Three consecutive validation batches, after the process change in March 2013, as
per the details given below were selected for the stability studies.

1. QN-13005 Mar 2013
2. QN-13006 Apr 2013
3. QN-13007 Apr 2013
Process validation batches as per the details given below are included in stability
studies.

1. QN-16033 Jul-2016
2. QN-16034 Jul-2016
3. QN-16035 Aug-2016
Following annual batches were included in the long term stability studies.
1. QN-14001 Jan-2014
2. QN-15001 Mar-2015
3. QN-16001 Jan -2016
4 QN-17001 Jan -2017
Subsequently one batch every year will be included in the long term stability
studies.
Data provided on following pages.
January, 2020 3.2.S.7.3 STABILITY DATA Page 1

•
Format No: QC/FM-186/00
Reference SOP No: QCS/015
Aarti Industries Limited Unit-IV, E-50, MIDC, Tarapur
Quality Control
I
Stability Study Report (Long-term)

Page I of 1
Product : Quinapril Hydrochloride (USP) Mfg. Date : MAY-2011

Batch No. : QN-11001 Storage condition : Temperature: 5°C + 3°C
Batch Size : 73.80Kg. Initiation Date : 01/08/11
Stability study protocol No. : QA/SB/P/QN-001 . Reason for Stability :Validation batch
Packing condition :Quinapril hydrochloride is packed in double polyethylene bags i.e. outer black antistatic polyethylene and inner natural antistatic polyethylene bags under nitrogen. These both
bags are twist tied and fastened using a fastener. These bags are placed in triple laminated sun barrier (TLSB) bags/pouches. They are placed in EPS boxes which are to simulate market condition.
Sr.No Test Limit Initial 3M 6M 9M 12M 18M 24M 36M 48M 60M
A white to off white powder, with pink White White White White White White White White White White
1 Description powder powder powder powder powder powder
cast at times powder powder powder powder
Water content
2 Not more than 1.0 % wlw 0.48% 0.55% 0.58% 0.60% 0.56% 0.61 °/o 0.64% 0.74% 0.77% 0.80%
(By KF)
Specific optical Between +14.4° and +15.4° at 25°C on
.
3
rotation anhydrous basis
+14.83 ° +14.93 ° +14.70 ° + 14.91 ° +14.84 ° +14.80 ° +14.73 ° + 14.92° +15.02° +14.97°
Related compound A : NMT 0.5o/o 0.12% 0.19% 0.18% 0.18% 0.21% 0.24% 0.21% 0.20o/o 0.23% 0.27%
Related compound B : NMT 0.5% 0.13% 0.13% 0.12% 0.13% •0.12% 0.15% 0.18% 0.11% 0.07% 0.10%
Related
4 Not Not Not Not Not Not Not Not Not Not
compounds N-acetyl quinaprilate : NMT 0.15%
detected detected detected detected detected detected detected detected detected detected
(By HPLC)
Any unknown impurity: NMT 0.10% 0.08% 0.06% 0.08% 0.07% 0.07% 0.06% 0.08% 0.08% 0.03% 0.05%
Total impurities : NMT 2.0% 0.47% 0.42% 0.49% 0.38% 0.52%. 0.48% 0.56% 0.59% 0.36% 0.59%
5 Assay (By Between 98.5% to 101.5% on the
99.73% 99.69% 99.71°/o 99.62% 99.72% 99.61% 99.74% 99.54% 99.20% 99.41%
HPLC) anhydrous basis.
Date of Analysis : ----
___ ..
05/11111 03/l0/12 09/05/12 06/08/12 06/02/13 05/08/13 04/09/14 11109/15 02/09/16
Analyzed By : UPS us PC ABP YK SRY BHS KBV KP
Remark:
--- - - -- --- ---~ -- -- -- --- ----- --- -- ----------------
_('Qfl!p!ie~ __ ...___Q>!!!.Ql ~s_ _ ~- j::Ql!!lJ!ie_L_..____fQrnQlLes~ _ -~('_QJ!!Jili~ ~Oll_lpl~s~ ~fllpl ieL_, COJ1]>~ _ i'ompl ie~_L__~OJnj)l i(!s_ ~
Conclusion : The product is stable up to 60 month as per specification number AQC/SP/SB/00 1 Revision No.OO at the mentioned storage condition.
Prepared by: Checked by: __'VZ~·.,____ Approved by:

(Sign/date) (Sign/date) o2--l o? \' b (Sign/date)

1
• Aarti Industries Limited Unit-IV, E-50, MIDC, Tara pur ~
Quality Control
Format No: QCIFJ\1-186/00 I Pag·e 1 of 1
Product : Quinapril Hydrochloride (USP) Mfg. Date : MAY-2011
Batch No. : QN-11002 Storage condition : Temperature: 5°C + 3°C
Batch Size : 75.30Kg. Initiation Date : 01/08/2011
Stability study protocol No. : QA/SB/P/QN-001 Reason for Stability :Validation batch
Sr.. No Test Limit Initial 3M 6M 9M 12M 18M 24M 36M 48M 60M
A white to off white powder, with White White White White White White White White White White
I Description
Qink cast at times powder · powder powder powder powder powder powder powder powder powder
Water content
2 Not more than 1.0 % w/w 0.65% 0.78% 0.81% 0.81% 0.81% 0.84 o/o ~75% 0.79% 0.81% 0.82%
(By KF) ----1
Specific optical Between +14.4° and +15.4° at 25°C
3 +15.03 ° +15.02 ° +14.79 ° + 15.22 ° +14.82 ° +14.85° +14.79° +14.82° +15.03° + 14.96°
I
rotation on anhydrous basis

. i
Related compound A : NMT 0.5% 0.20% 0.17% 0.24% 0.23% 0.19% 0.25% 0.20% 0.23% 0.23% 0.24%
Related compound B : NMT 0.5% 0.12% 0.13% 0.12% 0.15% 0.11% 0.15% 0.17% 0.11% 0.07% 0.10%
Related Not Not Not Not Not Not Not Not Not
4 N-acetyl quinaprilate : NMT 0.15% 0.02%
compounds detected detected detected detected detected detected detected detected detected
(ByHPLC)
Any unknown impurity : NMT
0.08% 0.07% 0.08% 0.07% 0.06% 0.06% 0.08% 0.09% 0.03% 0.05%
0.10%
Total impurities: NMT 2.0% 0.54% OAI% 0.530;(, 0.45% 0.50% 0.48% 0.54% 0.51% !().36% 0.50%
99.62% 99.80% 99.73%. 99.64% 99.73% 99.69% 99.73% 99.40% 99.36% 99.75%
.,.. ____
Date of Analysis: 05/11111 03/02/12 09/05/12 06/08/12 06/02/13 05/08/13 04/09/14 11109/15 02/09/16
Analyzed By : ----- UPS UPS PC ABP YK SRY BHS KBV KP
Remark: Complies Complies Complies Complies Comp1ies Complies Com_r_lies Complies Complies Complies
Conclusion :The product is stable up to 60 month as per specification number AQC/SP/SB/001 Revision No.OO at the mentioned storage condition.
~...,
~~~
--z;~l-(o:g (t--6
Checked by:-~""'-_,_______ Approved by:
Prepared by:
(Sign/date)
~~ (Sign/date) ot-t 1)~ l t k (Sign/date)

•
Format No: QC/FM-186/00
---------------
Quality Control
I
Stabili-ty Study Report (Long-term)

PaJ!e I of 1
Product : Quinapril Hydrochloride (USP) Mfg. Date : JUN-2011

Batch No. : QN-11003 Storage condition :Temperature: 5°C + 3°C
Batch Size :73.90 Kg Initiation Date : 01/08/2011
Stability study protocol No. : QA/SB/P/QN-001 Reason for Stability :Validation batch
A white to off white powder, with White White White White White White White White White White
1 Description
pink cast at times powder powder powder powder powder powder powder powder powder _j)owder
Water content
2 Not more than 1.0 % w/w 0.53% 0.59% 0.59% 0.59% 0.69% 0.72% 0.84% 0.84% 0.86% 0.82%
(By KF)
Specific optical Between +14.4° and +15.4° at 25°C
3 14.76 ° 14.99 ° 15.22 ° 15.08 ° 14.75 ° 14.85 ° 14.81 ° 14.86 ° 14.99° +14.96°
rotation on anhydrous basis
Related compound A : NMT 0.5% 0.20% 0.21% 0.23% 0.23%
.0.20% 0.24% 0.20% 0.25% 0.23% 0.20%
Related compound B: NMT 0.5% 0.12% 0.13% 0.12% 0.15% 0.11% 0.15% 0.17% 0.11% 0.07% 0.07%
Related Not Not Not Not Not Not Not Not Not
4 N-acetyl quinaprilate: NMT 0.15% 0.02%
compounds detected detected detected detected detected detected detected detected detected
(By HPLC)
Any unknown impurity : NMT
0.08% 0.08% 0.08% 0.07% 0.07% 0.06% 0.08% 0.09% 0.03% 0.06%
0.10%
Total impurities: NMT 2.0% 0.54% 0.44% 0.53% 0.45% 0.47% 0.48% 0.54% 0.54% ,{).36% 0.42%
99.58% 99.83% 99.79% 99.62% 99.77% 99.65% 99.65% 99.47% 99.34% 98.56%
Date of Analysis : ----- 05111111 03/02/12 09/05/12 06/08112 06/02/13 05/08/13 04/09114 11109/15 02/09/16
Analyzed By : ----- UPS UPS PC ABP YK SRY BHS KBV KP
Remark: Complies Complies Complies Complies Complies Complies Complies Complies Comp)ies Complies
Conclusion :The product is stable up to 60 month as per specification number AQC/SP/SB/001 Revision No.OO at the mentioned storage condition.
Prepared by: ~
(Sign/date) """"""C>~.G,
Checked by: _ _,_\f.,_,.____ __
(Sign/date) ~z.\ o91 t-'
Approved by:
(Sign/date)
~ ../(-6
•
Product
Aarti Industries Limited Unit-IV, E-50, MIDC, Taranur
: Quinapril Hydrochloride (USP)

Stability Study Report (Lon2-term)
Mfg. Date : JAN-2014
Batch No. : QN-14001 Storage condition : Temperature: 5°C ±3°C
Batch Size :87.50 Kg Initiation Date - - -
: 11/04/14
- -- ---- - -
Sr. No Test Limit Initial 3M 6M 9M 12M 18M 24M 36M 48M 60M
A white to off white powder, with White ·White White White White White White
1 Description
pink cast at times powder powder powder powder powder powder powder \ I
2
Water content
(By K.F)
Not more than 1.0 % w/w 0.89% 0.77% 0.79% 0.81% 0.84% 0.86% 0.85%
\ I
3
Specific optical.
rotation
Between +14.4° and +15.4° at
25°C on anhydrous basis
+14.67° +14.80° +15.00° +14.79° +14.64° +14.91° +14.67° \ I
Related com_pound A : NMT 0.5% 0.07% 0.15% 0.16% 0.18% 0.24% 0.27% 0.19% \ I
Related
Related compound B : NMT 0.5% 0.03% 0.04% 0.09% 0.06% 0.07% 0.08% 0.11%
v
4 compounds
(By HPLC)
N-acetyl quinaprilate: NMT
0.15%
Any unlmown impurity : NMT
Not
detected
Not
detected
Not
detected
Not
detected
Not
detected
Not
detected
Not
detected
I
1\ \
0.06% 0.06% 0.07% 0.06% 0.06% 0.04%
0.10%
0.07%
I \
Total ffi1purities : NMT 2.0% 0.18% 0.28% 0.47% 0.37% 0.46% 0.47% 0.48% L '\
5
Assay (By
HPLC)
Between 98.5% to 101.5% on the
anhydrous basis
Remark
99.56%
Comlies
99.37%
Com_Qlies
99.52% 99.64%
~omp!~- ~omplies
99.72%
Compl~s_ L_
99.89%
_Qomplies _
99.29%
ComQli~s /
I- -
\ '\'
Conclusion: The above product is stable up to above months at the mentioned storage condition and further study is in progress.
Packing condition: Quinapril hydrochloride·is packed in double polyethylene bags i.e. outer black antistatic polyethylene and inner natural antistatic polyethylene bags
under nitrogen. These both bags are twist tied and fastened using a fastener. These bags are placed in triple laminated sun barrier (TLSB) bags/pouches. They are placed
in EPS boxes which are to simulate market condition.
Prepared By:
(Sign/date)
~
\ ~' b~-\ \G
Checked By:
(Sign/date)
~~\~
\. ~
Approved By:
(Sign/date)
kA~
)4 0

•
Product
: Quinapril Hydrochloride (USP) Mfg. Date : Mar-2015
Batch No. : QN-15001 Storage condition : Temperature: 5°C ± 3°C
Batch Size :85.50 kg. Initiation Date : 06/05/15 --
A white to off white powder, with A White A White A White A White A White
1 Description
3
Specific optical
rotation
Water content
(By K.F)
pink cast at times
Between+ 14.4° and+ 15.4° at
25°C on anhydrous basis
Not more than 1.0% w/w
J~owder
+14.92 °
0.80%
powder
+14.62 °
0.80%
powder
+14.71 °
0.83%
powder
+14.71 °
0.85%
powder
+14.63 °
0.84%
"" ~
~ v
/
/
v
/
Related compound A : NMT 0.5% 0.21% 0.25% 0.24% 0.19% 0.24%

I
Related
Related compound B : NMT 0.5%. 0.05% 0.05% 0.08% 0.10% 0.08%
""" ~
4 compounds
(ByHPLC)
N-acetyl quinaprilate: NMT
0.15%
Not
detected
Not
detected
Not
detected
Not detected
Not
detected L
v ~ I
L ~
Any unknown impurity: NMT
0.08% 0.09% 0.04% 0.06% 0.07%
0.10%
Total impurities : NMT 2.0% 0.37% 0.44% 0.44% 0.46% 0.51% .. v
5
Assay (By
HPLC)
Between 98.5% to 101.5% on the
anhydrous basis
Remark
99.49% 99.27% 100.19% 99.59% 99.27%
Complies _....._/
/ ""~
Complies Complies Complies Complies -
"
Conclusion: The above product is stable up to above months at the mentioned storage condition and further study is in progress.
Packing condition: Quinapril hydrochloride is packed in double polyethylene bags i.e. outer black antistatic polyethylene and inner natural antistatic polyethylene bags
under nitrogen. These both bags are twist tied ·and fastened using a fastener. These bags are placed in triple laminated sun barrier (TLSB) bags/pouches. They are placed
in EPS boxes which are to simulate market condition.
Prepared By: 5i§'t Checked By: ~~;;:\ Approved By: ~( /

(Sign/date) e \\ 1lC \ l"' (Sign/date) . e~ oc..; \G (Si~date) o12/o~ (~

QN - USP - Rev 06

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QUINAPRIL HYDROCHLORIDE USP

OPEN PART FOR

AARTI INDUSTRIES LIMITED

Section Details Pages

January, 2020 3.1 TABLE OF CONTENTS Page 1

Quinapril Hydrochloride belongs in a class of drugs called angiotensin converting

The effect of quinapril in hypertension and in congestive heart failure (CHF)

The FDA approved Quinapril Hydrochloride in 1991.

January, 2020 3.2.S.1 GENERAL INFORMATION Page 1

International Quinapril Hydrochloride

January, 2020 3.2.S.1.1 NOMENCLATURE Page 1

MOLECULAR FORMULA : C25H30N2O5.HCl

MOLECULAR MASS : 474.98

January, 2020 3.2.S.1.2 STRUCTURE Page 1

Description White to off white powder, with pink cast at

* Reference: Merck Index, 13th edition, 8139, page 1441.

January, 2020 3.2.S.1.3 GENERAL PROPERTIES Page 1

January, 2020 3.2.S.2 MANUFACTURE Page 1

Name and address of the manufacturing and testing site:

Aarti Industries Limited

FEI Number: 3005256484

Mr. Shyamsundar Desai (DGM QA&QC)

January, 2020 3.2.S.2.1 MANUFACTURER Page 1

3.2.S.2.2.1 BRIEF DESCRIPTION OF THE MANUFACTURING PROCESS

Manufacturing of Quinapril hydrochloride involves two steps.

Step I: Benzyl Quinapril Maleate:

January, 2020 3.2.S.2.2 DESCRIPTION OF MANUFACTURING Page 1

Step II: Quinapril Hydrochloride

January, 2020 3.2.S.2.2 DESCRIPTION OF MANUFACTURING Page 2

Step I: Benzyl Quinapril Maleate

Benzyl Quinapril Maleate (QN-III)

Step II: Quinapril Hydrochloride

January, 2020 3.2.S.2.2 DESCRIPTION OF MANUFACTURING Page 3

Step I: Benzyl Quinapril Maleate

Saturated sodium bicarbonate solution Reaction M ass Sample for pH

Potable water Organic Layer

AC compound Reaction M ass

January, 2020 3.2.S.2.2 DESCRIPTION OF MANUFACTURING Page 4

Sample for TLC

Saturated sodium Organic Layer

Potable Water Organic Layer

January, 2020 3.2.S.2.2 DESCRIPTION OF MANUFACTURING Page 5

Maleic acid solution Organic Layer

Ethyl acetate and acetone washing Wet cake

Ethyl acetate and acetone

Ethyl acetate Wet cake

Ethyl acetate Wet cake

January, 2020 3.2.S.2.2 DESCRIPTION OF MANUFACTURING Page 6

Sodium carbonate Reactor

Benzyl Quinapril Maleate

Aqueous Layer ETP

Potable water Organic Layer

Sodium sulphate Organic Layer

January, 2020 3.2.S.2.2 DESCRIPTION OF MANUFACTURING Page 7

Filtrate Check clarity

Reaction mass Check clarity

DF Flushing Sample for HPLC

January, 2020 3.2.S.2.2 DESCRIPTION OF MANUFACTURING Page 8

DF Thick Mass Check clarity

Jet milled Material

Drying (VTD) in 2 lots

Drying (VTD) in 2 lots