Printed on: Fri Aug 25 2023, 10:53:22 AM(EST) Status: Currently Official on 25-Aug-2023 DocId: GUID-F7682879-7EF1-4B54-A68B-8EBFD365B0AA_5_en-US

Printed by: Alejandro Restrepo Official Date: Official as of 01-May-2022 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: m7o6q DOI: https://doi.org/10.31003/USPNF_M12530_05_01
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Injection volume: 2 µL
Carbamazepine System suitability
Samples: System suitability solution and Standard solution
Suitability requirements
Resolution: NLT 1.7 between carbamazepine related
compound A and carbamazepine, System suitability
solution
C15H12N2O 236.27 Tailing factor: NMT 2.0, Standard solution
5H-Dibenz[b,f]azepine, 5-carboxamide; Relative standard deviation: NMT 0.73%, Standard
5H-Dibenz[b,f]azepine-5-carboxamide CAS RN®: 298-46-4; solution
UNII: 33CM23913M. Analysis
DEFINITION Samples: Standard solution and Sample solution
Carbamazepine contains NLT 98.0% and NMT 102.0% of Calculate the percentage of carbamazepine (C15H12N2O) in
carbamazepine (C15H12N2O), calculated on the dried basis. the portion of Carbamazepine taken:

IDENTIFICATION Result = (r U/r S) × (C S/C U) × 100

• A. SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared
Spectroscopy: 197M rU = peak response from the Sample solution
• B. The retention time of the major peak of the Sample rS = peak response from the Standard solution
solution corresponds to that of the Standard solution, as CS = concentration of USP Carbamazepine RS in the
obtained in the Assay. Standard solution (mg/mL)
CU = concentration of Carbamazepine in the Sample
ASSAY

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solution (mg/mL)
• PROCEDURE
Solution A: Add 0.5 mL of triethylamine and 0.5 mL of Acceptance criteria: 98.0%–102.0% on the dried basis
formic acid to 1000 mL of water.
Solution B: Add 0.25 mL of formic acid to 1000 mL of IMPURITIES
methanol.
ci • CHLORIDE AND SULFATE, Chloride á221ñ
Mobile phase: See Table 1. Sample solution: Boil 1.0 g of Carbamazepine in 20.0 mL
of water for 10 min, cool, adjust the volume to 20 mL, and
Table 1 filter. Use a 10.0-mL portion of the filtrate.
Time Solution A Solution B Acceptance criteria: 0.014%; the Sample solution contains
(min) (%) (%) no more chloride than corresponds to 0.10 mL of 0.020 N
ffi
hydrochloric acid.
0.0 80 20
• RESIDUE ON IGNITION á281ñ
3.0 80 20 Sample: 2.0 g of Carbamazepine
Acceptance criteria: NMT 0.1%
12.0 60 40
• ORGANIC IMPURITIES
18.0 45 55 Solution A, Solution B, Mobile phase, Diluent, and
O

20.0 45
20.1 80
23.0 80
Diluent: Methanol and water (50:50)
System suitability stock solution: 0.02 mg/mL each of USP
Carbamazepine RS and USP Carbamazepine Related
Compound A RS prepared as follows. First dissolve the
Reference Standards in 50% of the final flask volume of
methanol, then dilute with water to volume.
System suitability solution: 0.002 mg/mL each of USP
Carbamazepine RS and USP Carbamazepine Related
Compound A RS from System suitability stock solution in
Diluent
Standard solution: 0.1 mg/mL of USP Carbamazepine RS
prepared as follows. First dissolve the Reference Standard in
50% of the final flask volume of methanol, then dilute with
water to volume.
Sample solution: 0.1 mg/mL of Carbamazepine prepared
as follows. First dissolve the sample in 50% of the final flask
volume of methanol, then dilute with water to volume. Pass
through a suitable filter of 0.2-µm pore size.
Chromatographic system
(See Chromatography á621ñ, System Suitability.)
Mode: LC
Detector: UV 230 nm
Column: 2.1-mm × 10-cm; 1.8-µm packing L10
Column temperature: 40°
Flow rate: 0.3 mL/min
55
Chromatographic system: Proceed as directed in the
Assay.
20 Standard stock solution: 0.02 mg/mL each of USP
20
Carbamazepine RS, USP Carbamazepine Related
Compound A RS, and USP Carbamazepine Related
Compound B RS, prepared as follows. First dissolve the
Reference Standards in 50% of the final flask volume of
methanol, then dilute with water to volume.
Standard solution: 0.002 mg/mL each of USP
Carbamazepine RS, USP Carbamazepine Related
Compound A RS, and USP Carbamazepine Related
Compound B RS from Standard stock solution in Diluent
Sample solution: 1.0 mg/mL of Carbamazepine prepared
as follows. First dissolve the sample in 50% of the final flask
volume of methanol, then dilute with water to volume. Pass
through a suitable filter of 0.2-µm pore size.
System suitability
Sample: Standard solution
Suitability requirements
Resolution: NLT 1.7 between carbamazepine related
compound A and carbamazepine
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of each specified impurity in the
portion of Carbamazepine taken:
Result = (r U/r S) × (C S/C U) × 100
rU = peak response of each specified impurity from the
Sample solution

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Printed on: Fri Aug 25 2023, 10:53:22 AM(EST) Status: Currently Official on 25-Aug-2023 DocId: GUID-F7682879-7EF1-4B54-A68B-8EBFD365B0AA_5_en-US
Printed by: Alejandro Restrepo Official Date: Official as of 01-May-2022 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: m7o6q DOI: https://doi.org/10.31003/USPNF_M12530_05_01
2

rS = peak response of the corresponding USP SPECIFIC TESTS

Reference Standard from the Standard solution • ACIDITY
CS = concentration of the corresponding USP Sample solution: 50 mg/mL of Carbamazepine in water
Reference Standard in the Standard solution (mg/ prepared as follows. Mix 2.0 g of Carbamazepine in
mL) 40.0 mL of water for 15 min, and filter through paper.
CU = concentration of Carbamazepine in the Sample Analysis: To a 10.0-mL aliquot of Sample solution add 1 drop
solution (mg/mL) of phenolphthalein TS, and titrate with 0.01 N sodium
hydroxide VS. Perform a blank determination, and make
Calculate the percentage of each individual unspecified any necessary correction.
impurity in the portion of Carbamazepine taken: Acceptance criteria: NMT 1.0 mL of 0.01 N sodium
hydroxide VS is required for each 1.0 g of Carbamazepine.
Result = (r U/r S) × (C S/C U) × 100 • ALKALINITY
Sample solution: 50 mg/mL of Carbamazepine in water
rU = peak response of each unspecified impurity prepared as follows. Mix 2.0 g of Carbamazepine in
from the Sample solution 40.0 mL of water for 15 min, and filter through paper.
rS = peak response of carbamazepine from the Analysis: To a 10.0-mL aliquot of Sample solution add 1 drop
Standard solution of methyl red TS, and titrate with 0.01 N hydrochloric acid
CS = concentration of USP Carbamazepine RS in the VS. Perform a blank determination, and make any necessary
Standard solution (mg/mL) correction.
CU = concentration of Carbamazepine in the Sample Acceptance criteria: NMT 1.0 mL of 0.01 N hydrochloric
solution (mg/mL) acid VS is required for each 1.0 g of Carbamazepine.
• LOSS ON DRYING á731ñ
Acceptance criteria: See Table 2. Disregard any impurity Analysis: Dry at 105° for 2 h.

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peak less than 0.05%. Acceptance criteria: NMT 0.5%
Table 2
Change to read:
Relative Acceptance
Retention Criteria, • ▲X-RAY POWDER DIFFRACTION á941ñ▲ (CN 1-May-2022): The
Name
Carbamazepine related
compound Aa
Time

0.96
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NMT (%)

0.2
X-ray diffraction pattern conforms to that of USP
Carbamazepine RS, similarly determined.
ADDITIONAL REQUIREMENTS
Carbamazepine 1.00 — • PACKAGING AND STORAGE: Preserve in tight containers.
• USP REFERENCE STANDARDS á11ñ
ffi
Carbamazepine related
compound Bb 1.45 0.2 USP Carbamazepine RS
USP Carbamazepine Related Compound A RS
Individual unspecified impurity — 0.2
10,11-Dihydrocarbamazepine.
Total impurities — 0.5 C15H14N2O 238.28
USP Carbamazepine Related Compound B RS
a 10,11-Dihydrocarbamazepine.
O

b 5H-Dibenz[b,f]azepine.
5H-Dibenz[b,f]azepine.
C14H11N 193.24

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