Carbamazepine

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₁₅H₁₂N₂O   236.27

A (USP 1-Dec-2023)

5H-Dibenz[b,fazepine-5-carboxamide CAS RN: 298-46-4; UNII: 33CM23913M.

1 DEFINITION

Carbamazepine contains NLT 98.0% and NMT 102.0% of carbamazepine (C₁₅H₁₂N₂O), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M or 197A (USP 1-Dec-2023)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

PROCEDURE

Solution A: Add 0.5 mL of triethylamine and 0.5 mL of formic acid to 1000 mL of water.

Solution B: Add 0.25 mL of formic acid to 1000 mL of methanol.

Mobile phase: See Table 1.

Table 1

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. Transfer suitable amounts of USP Carbamazepine RS and USP Carbamazepine Related Compound A RS to a suitable volumetric flask. Add 50% of the flask volume of methanol to dissolve (USP 1-Dec-2023) 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 the System suitability stock solution in Diluent

Standard solution: 0.1 mg/mL of USP Carbamazepine RS prepared as follows. Transfer a suitable amount of USP Carbamazepine RS to a suitable volumetric flask. Add 50% of the flask volume of methanol to dissolve (USP 1-Dec-2023) Dilute with water to volume.

Sample solution: 0.1 mg/mL of Carbamazepine prepared as follows. Transfer a suitable amount of sample to a suitable volumetric flask. Add 50% of the flask volume of methanol to dissolve (USP 1-Dec-2023) Dilute with water to volume. Pass through a suitable filter of 0.2-umfipore size

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 2.1-mm x 10-cm; 1.8-µm packing 110

Column temperature: 40"

Flow rate: 0.3 mL/min

Injection volume: 2 µL

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

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of carbamazepine (C₁₅H₁₂N₂O) in the portion of Carbamazepine taken:

Result = (r_U/r_S) x (C_S/C_U) ×100

r_U = peak response of carbamazepine (USP 1-Dec-2023) from the Sample solution

r_S = peak response of carbamazepine (USP 1-Dec-2023) from the Standard solution

C_S = concentration of USP Carbamazepine RS in the Standard solution (mg/mL)

C_U = concentration of Carbamazepine in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 CHLORIDE AND SULFATE (221), Chloride

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 filter. Use a 10.0-mL portion of the filtrate.

Acceptance criteria: 0.014%; the Sample solution contains no more chloride than corresponds to 0.10 ml of 0.020 N hydrochloric acid.

4.2 RESIDUE ON IGNITION (281)

4.3 Sample: 2.0 g of Carbamazepine

Acceptance criteria: NMT 0.1%

Change to read:

4.4 ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity stock solution: 0.03 mg/mL each of USP Carbamazepine RS, USP Carbamazepine Related Compound A RS, and USP Carbamazepine Related Compound B RS, prepared as follows. Transfer suitable amounts of USP Carbamazepine RS, USP Carbamazepine Related Compound A RS, and USP Carbamazepine Related Compound. B.RS to a suitable volumetric flask. Add 50% of the flask volume of methanol to dissolve. Dilute with water to volume.

Sensitivity solution: 0.0003 mg/mL each of USP Carbamazepine RS. USP Carbamazepine Related Compound A RS, and USP Carbamazepine Related Compound B. RS from the Sensitivity stock solution in Diluent (USP 1-Dec-2023)

Standard stock solution: 0.03 mg/mL of USP Carbamazepine RS, and 0.05 mg/mL each of USP Carbamazepine Related Compound A RS and USP Carbamazepine Related Compound B RS, prepared as follows. Transfer a suitable amount of USP Carbamazepine RS, USP Carbamazepine Related Compound A RS. and USP Carbamazepine Related Compound B.RS to a suitable volumetric flask. Add 50% of the flask volume of methanol to dissolve (USP 1-Dec-2023) Dilute with water to volume.

Standard solution: 0.0006 (USP 1-Dec-2023) mg/mL (USP 1-Dec-2023) of USP Carbamazepine RS, and 0.001 mg/mL each of (USP 1-Dec-2023) USP Carbamazepine Related Compound A RS and USP Carbamazepine Related Compound B RS from the Standard stock solution in Diluent

Sample solution: 1.0 mg/mL of Carbamazepine prepared as follows. Transfer a suitable amount of sample to a suitable volumetric flask. Add 50% of the flask volume of methanol to dissolve (USP 1-Dec-2023) Dilute with water to volume. Pass through a suitable filter of 0.2-um pore size.

System suitability

Samples: Sensitivity solution and (USP 1-Dec-2023) Standard solution

Suitability requirements

Resolution: NLT 1.7 between carbamazepine related compound A and carbamazepine, Standard solution (USP 1-Dec-2023)

Relative standard deviation: NMT 5.0% for carbamazepine, carbamazepine related compound A, and carbamazepine related compound B, Standard solution

Signal-to-noise ratio: NLT 10 for carbamazepine, carbamazepine related compound A, and carbamazepine related compound B, Sensitivity solution (USP 1-Dec-2023)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of carbamazepine related compound A and carbamazepine related compound BA (USP 1-Dec-2023) in the portion of Carbamazepine taken:

Result = (r_U/r_S) x (C_S/C_U) ×100

r_U = peak response of carbamazepine related compound A or carbamazepine related compound BA (USP 1-Dec-2023) from the Sample solution

r_S = peak response of the corresponding USP Reference Standard from the Standard solution

C_S = concentration of the corresponding USP Reference Standard in the Standard solution (mg/mL)

C_U = concentration of Carbamazepine in the Sample solution (mg/mL)

Calculate the percentage of any (USP 1-Dec-2023) unspecified impurity in the portion of Carbamazepine taken:

Result = (r_U/r_S) x (C_S/C_U) ×100

r_U = peak response of any (USP 1-Dec-2023) unspecified impurity from the Sample solution

r_S = peak response of carbamazepine from the Standard solution

C_S = concentration of USP Carbamazepine RS in the Standard solution (mg/mL)

C_U = concentration of Carbamazepine in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.03% (USP 1-Dec-2023)

Table 2

5 SPECIFIC TESTS

5.1 ACIDITY

Sample solution: 50 mg/mL of Carbamazepine in water prepared as follows. Mix 2.0 g of Carbamazepine in 40.0 mL of water for 15 min, and filter through paper.

Analysis: To a 10.0-mL aliquot of Sample solution add 1 drop of phenolphthalein TS, and titrate with 0.01 N sodium hydroxide VS. Perform a blank determination, and make any necessary correction.

Acceptance criteria: NMT 1.0 mL of 0.01 N sodium hydroxide VS is required for each 1.0 g of Carbamazepine.

5.2 Alkalinity

Sample solution: 50 mg/mL of Carbamazepine in water prepared as follows. Mix 2.0 g of Carbamazepine in 40.0 mL of water for 15 min, and filter through paper.

Analysis: To a 10.0-mL aliquot of Sample solution add 1 drop of methyl red TS, and titrate with 0.01 N hydrochloric acid VS. Perform a blank determination, and make any necessary correction.

Acceptance criteria: NMT 1.0 mL of 0.01 N hydrochloric acid VS is required for each 1.0 g of Carbamazepine.

5.3 Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 0.5%

X-Ray Diffraction 〈941〉: The X-ray diffraction pattern conforms to that of USP Carbamazepine RS, similarly determined.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

Change to read:

USP Reference Standards 〈11〉

USP Carbamazepine RS

USP Carbamazepine Related Compound A RS

10,11-Dihydro-5H-dibenz[b,f]azepine-5-carboxamide. (USP 1-Dec-2023)

C₁₅H₁₄N₂O 238.29 (USP 1-Dec-2023)

USP Carbamazepine Related Compound B RS

5H-Dibenz[b,f]azepine.

C₁₄H₁₁N 193.25 (USP 1-Dec-2023)