Calculation of

Pharmaceutical Analysis
Preparation calculation

Titration calculation
Typical calculation
15/09/56

 (Calculation
of Pharmaceutical Analysis)

(Preparation calculation)

(Titration calculation)

(Typical calculation)
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Volumetric analysis
Gravimetric analysis


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Volumetric titration
Direct

titration
Residual titration (Back titration )

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( Direct titration)
flask Analyte
Active ingredient
analyte Titrant
buret buret
titrant Titration

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Direct titration(cont.)
analyte titrant
Stoichiometric point
Equivalent point
End point
stoichiometric point
Indicator
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 (Residual
titration or back titration)

residual titration back titration

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15/09/56

 Pharmaceutical Analysis
( )

(double check)
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(Units and Expression of Concentration)
MW. ( mol. Wt.)=
molecular weight
mole
=
a gram molecular weight
moles
=
number of moles
=
wt. in g / MW
m mole
=
number of millimoles
=
wt. in mg/ MW
M, Molarity
=
the number of moles of
solutes contained in 1 L(1000ml) of
solution
= the number of m moles of solutes
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10


moles

Molarity(M)

moles

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gram
molecular weight
g
MW
moles
L
g
/L
MW
MxL

m moles

Molarity(M)

m moles

milligram
molecular weight
mg
MW
m moles
mL
mg
/ mL
MW
M x mL

11

MW
EW, eq.wt., equivalent weight =
+
no.of H from 1 mol. acid
MW
=
no.of H + 1 mol. base
MW
=
no.of ion from 1 mol.
MW
=
no.of electron change to 1 mol.

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12

eq., equivalents

=
no. of equivalents
=
wt in g / EW
meq. Milliequivalents =
no. of milliequivalents
=
wt in mg / EW
N , Normality
=
the no. of equivalents
of solute contained in 1 L(1000ml) of solution
=
the no. of milliequivalents
of solute contained in 1 ml of solution

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13


equivalents

eq
Normality

eq

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gram
equivalent weight
g
MW
eq
L
g
/L
EW
NxL

milliequivalent
meq
Normality

meq

milligram
equivalent weight
mg
MW
meq
mL
mg
/ mL
EW
N x mL

14


SI Units
(International System of Units)
cm3, dm3,
(USP)


complexometric titration
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15

 (Preparation
calculation)
(volumetric solution, VS
standard solution)


1
Preparation and standardization of
1 N H2SO4 solution
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16

 1
sulfuric acid, Normal(1N)
sulfuric acid 15 ml
510 ml
sulfuric acid

( H2SO4 MW 98.07 1.83
95% )
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17

1 N H2SO4 1 H2SO4 1 eq
eq =
g /EW
EW =
MW / 2
eq =
g x 2 / MW
g
=
1 x MW /2 = 98.07 /2 = 49.04
H2SO4 49.04 g 1 L 24.52 g 500 ml
g 100 24.52 100 14.10 ml
D

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1.83

95

18

sulfuric acid14.10 ml
sulfuric acid 15 ml

15 500
=
= 535 ml
14.1

535 15 = 520 ml

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19

hydrochloric
acid Tenth-Normal (0.1 N)
HCl MW 36.46 1.18 HCl 36 %

0.1 N hydrochloric acid 1 L HCl 1 eq
g
g
eq
=
=

EW
MW
g

= 0.1 MW = 0.1 36.46 = 3.646

HCl 3.646 g 1 L
g 100
3.646 100
=

= 8.5 ml

D %
1.18 36
hydrochloric acid 8.5 mlV.F.
1 L
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20

(Titration calculation)
3
1. (volume) (millilitre)
2. (Concentration)
Normality, N Molarity, M
3. (equivalent factor) (analyte)

(molecular weight, MW)

(equivalent weight, EW)
(Titer)
()1
mg = ml x N M x equivalent factor
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21

 3
mg
= ml x Molarity x molecular weight
2. mg
= ml x Normality x equivalent weight
3. mg
= ml x (Molarity or Normality) x Titer

(Standardization)

(no. of meq)
(solute) (Titrant)
(analyte)

1.

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22


meq of titrant

meq of analyte

N x ml

mg analyte
EW analyte

N x ml
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mg analyte
Titer

23

15/09/56

24

A Titrant
B Analyte(
)
C
analyte
analyte

()
2 3
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25



meq of titrant
NA mlA
NA
or
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NA

= meq of analyte
mgB
=
EWB
mgB
=
(EWB)(mlA)
=

mgB
(Titer)(mlA)
26

sodium
hydroxide primary standard
potassium biphthalate( 204.2)
0.8168 sodium hydroxide
phenolphthalein indicator
41.03 ml
Normality of NaOH
Normality of NaOH
Normality of NaOH

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N of NaOH

mg potassium biphthalate

EW mlA
816.8

204.2 41.03
0.0974896

0.09749

27

(standardization)
hydrochloric acid,
Normal (1 N)
primary standard anhydrous sodium carbonate
(Na2CO3 105.99) Each 52.99 mg
of anhydrous sodium carbonate is equivalent to
1 ml of 1 N hydrochloric acid
Titer (1 N HCl)(1 ml) 1 meq.
HCl 1 meq. Na2CO3 52.99 mg Na2CO3
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28

Na 2 CO3 52.99 mg

= 1 meq

mgNa 2 CO3
Na 2 CO3 in analyte weighed =
meq
52.99
mgNa 2 CO3
(N HCl)(ml HCl)
=
52.99
mgNa 2 CO3
N HCl
=
52.99(mlHCl)

Normality
NA
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mg standard
=
Titer ml titrant
mg B
=
(Titer)(ml A )

29

Titer
Na2CO3 + 2HCl
105.99

EW
EW Na 2 CO3

Titer

1 meq

M.R.

2NaCl + H2O + CO2

MW
=
no of H + 1 mol base
105.99
=
= 52.99 g/eq or mg/meq
2
= 52.99 mg/meq
= 52.99 mg Na 2 CO3 equivalent factor

(1ml HCl)(1 N HCl) = 52.99 mg Na 2 CO3

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30

 3 2
BP TP Each 52.99 mg
of Na2CO3 is equivalent to 1 ml 1
M hydrochloric acid
1mol Na 2CO3

= 2 moles HCl

1
moleNa 2 CO3 = 1 mole HCl
2
105.99
mgNa 2 CO3 = 1 m mole HCl 1ml 1 M
2
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31

 2 3 Na2CO3
1.4820 g titrant 28.10 ml

1.4820
Normality or Molarity =
52.9928.10
= 0.9953

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32



(secondary standard)

N1V1

(NA)(mlA)
NA
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N2V2

(NC)(mlC)

(NC)(mlC)
mlA
33

 4
sulfuric acid
sodium hydroxide
0.1050 N titrant sulfuric acid
25.00 ml titrant (NaOH) 23.45 ml
Normality of H 2SO 4

(N NaOH)(ml NaOH)
ml H 2SO 4

0.1050 23.45
25.00
0.09849

Normality of H 2SO 4

Molarity of H 2SO 4
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0.09849
0.04924
2
34



Rubric
purity rubric (% w/w)
meq of analyte

meq of titrant

mg B
EWB
mgB

(NA)(mlA)(EWB)

(NA)(mlA)

% purity B(as it weight)

% purity B(as it weight)

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(NA)(mlA)(EWB)
100
mg of sample taken
x
35

 ( )
rubric
percent calculated -on anhydrous -on dried
basis percent purity
percent of water
content percent of loss on drying

x
% content calculated on anhydrous basis
100
100 - L
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36

 2
percent of it weight

calculated on
anhydrous basis

Titer

(NA)(mlA) Titer
% Purity B(as it weight) =
100
mg of sample taken

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37

 5
potassium bicarbonate 0.2212 g
Titrate with 0.1091 N HCl. 20.23 ml
(EW KHCO3=100.1, . Titer = each ml of
0.1 N HCl equivalent to 10.01 mg of KHCO3)
mg of KHCO 3

(NHCl)(ml HCl)(EW KHCO 3 )

% purityKHCO 3
% purityKHCO 3

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(NHCl)(ml HCl)(EW KHCO 3 )

100
mg of sample taken
0.1091 20.23 100.1
100 99.98
221.2
38

 5 ( )
or mg KHCO3
% purity

15/09/56

= (N HCl)(ml HCl)(Titer)

10.01 100

= 0.1091 20.23
0.1 221.2
= 99.98

39


(Calculation of active
ingredient in dosage form)

(2.2)
20
( T)


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40

 (Tablets)
mgB
mgB/tab
or
% L.A.

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= (NA)(mlA)(equivalent factor)

T
= (NA)(mlA)(EWB)
g.sample taken
T
= (NA)(mlA)(TiterB)
g.sample taken
mg found
100
=
mg labeled

41

 (potent drug)
(dose) 50 mg

(Content uniformity)
20
mg B/tab = (NA)(mlA)(equivalent factor)

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42

 6
sodium bicarbonate tablet
300 mg
20
= 7.2540 g
(T)
=
0.3627 g

= 2.5210 g
0.9953 N HCl
=
24.20
ml
Titer sulfuric acid 1 N1 ml
sodium bicarbonate 84.01 mg
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43

 6 ()
mg NaHCO3 / tab

% L.A.

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T
= (NHCL)(mlHCL)(Titer)
g. sample
0.3627
= 0.9953 24.20 84.01
2.5210
= 291.1
291.1
=
100
300
= 97.03

44

 (Solution, Syrup)

300 15
4.0% w/v 4.0 100

mgB in V taken (NA)(mlA) (equivalent factor)

V labeled
mgB in V labeled (NA)(mlA) (equivalent factor)
V taken
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45

 7
sodium chloride
sodium chloride injection 0.9 % w/v
pipet 10.0 0.1011 N
Silver nitrate V.S. 15.20
(Titer 1 ml 0.1 N AgNO3 is

equivalent to NaCl 5.844 mg)

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46

 7 ( )
5.844
= 0.1011 15.20
mg NaCl
0.1

= 0.9% w/v 0.9 100
5.844 100
1
g. NaCl in 100 ml = 0.1011 15.20

0.1 10 1000
= 0.8081
% L.A.
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0.8981
=
100 = 99.79
0.9

47

 ( Suspension)
(take
sample) pipet
pipet

pipet
(weight
per ml)
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48

 ( Suspension) ( )


volumetric flask (W1)
()
(W2)
(W2 - W1)
volumetric flask
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49

 ( Suspension) ( )
W2 -W1
V
g of sample taken
V of sample taken =
Sp.gr.

Sp.gr.

mgB in V labeled

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V. labeled
= (NA)(mlA)(equivalent factor)
V.sampl taken
V.labeled Sp.gr.
= (NA)(mlA)(equivalent factor)
g sample taken

50

 weight per ml
volumetric flask (w1)
(w2)
w 2 - w1
weight per ml(wt/ml)

v
g of sample taken
volume of sample taken
wt/ml
V labeled
mgB in V labeled (NA)(mlA)(EW)
V sample taken
V labeled wt//ml
mgB in V labeled (NA)(mlA)(EW)
g sample taken
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51

(Residual titration)

Residual titration

determination)
relationship)
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(blank
(volume
52

1. Analyte B + Standard Solution C=50.0

ml
water bath 15 mins.
titrate (standard solution C excess )with
titrant A = a ml

2. Blank determination(volume
relationship). Pipet standard solution C =
50 ml.
titrate with titrant A= b ml

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53

Diagram of Back titration or

Residual titration for calculation

Analyte B
Standard solution C added

(Titrant A = standard solution C added)

Titrant A

(standard solution C excess)

(Titrant A = standard solution C excess)
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54

b titrant A added standard C

a titrant A remained standard C

b-a titrant A standard C analyte B

meq analyte B = meq titrant A = (b-a) NA
mg analyte B = (b-a)(NA)equivalent factor
(standardization)
C
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55

normality of standard solution C

Standard solution C = c ml

N1xV1 =N2x V2

NC =(NA x VA)/VC
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56

Residual titration standard C

volume relationship
titrant A b ml

standard C

ml

c
standard C a ml
titrant A a ml
b
c
titrant A (b - a) ml standard C c - ( a) ml
b
meq analyte B meq titrant A meq standard C

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c
meq analyte B NC[ c - ( a)]
b
c
mq analyte B NC[ c - ( a)] equivalent factor
b

57


volume
relationship
(error)
meq of analyte B = meq C added meq titrant A
meq of analyte B = [(N C x mlC)] [(N A x mlA)]

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58

15/09/56

59


Aspirin C9H8O4
residual titration( each ml 0.5 N NaOH
equivalent to 45.04 mg of C9H8O4)

= 1.4948 g
0.5010 N NaOH
= 50.0ml (c)
( 10 pp TS )
0.4890N H2SO4
= 17.20ml (a)
Loss on drying (L)
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0.4 %
60

meq of NaOH
meq of H2SO4

= 50 x 0.5010
= 17.20 x 0.4890

= 25.05
= 8.4108

meq of aspirin = 25.05 8.4108

=16.6392
mg aspirin
= meq x titer/0.5
= 16.6392x 45.04/0.5 =1498.9
%aspirin
= 1.4989/1.4948 x100 =100.3
%aspirin(dried) = 100.3/(100-0.4) x100
=100.7
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61

Aspirin C9H8O4
residual titration( each ml 0.5 N NaOH
equivalent to 45.04 mg of C9H8O4)

= 1.4948 g
0.5 N NaOH
= 50.0 ml
( 10 pp TS )
25.0 ml NaOH =0.4890N H2SO4 = 25.60 ml(b/2)
0.4890N H2SO4
= 17.20 ml (a)
Loss on drying (L)
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0.4 %
62

meq H2SO4

= 0.4890( b-a) = meq aspirin

meq of aspirin = 0.4890(51.20 -17.20) = 16.626

mg aspirin
= meq x titer/0.5
= 16.626x 45.04/0.5 =1497.67
%aspirin
= 1.4977/1.4948 x100 =100.2
%aspirin(dried) = 100.2/(100-0.4) x100
=100.6
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63

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64