Carbamazepine Oral Suspension

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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1 DEFINITION

Carbamazepine Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of carbamazepine (C₁₅H₁₂N₂O).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197S (CN 1-May-2020)

Sample solution: Place 5 mL of Oral Suspension in a separator containing 20 mL of 0.1 N sodium hydroxide, and extract with 25 mL of chloroform. Pass the extract through anhydrous sodium sulfate supported on filter paper into a beaker. Wash the anhydrous sodium sulfate with 10 mL of chloroform, and add the washing to the extract. Evaporate the chloroform extract to dryness with the aid of a stream of nitrogen. Dissolve the residue in 10 mL of methylene chloride.

Acceptance criteria: Meets the requirements

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

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

System suitability solution: 0.002 mg/mL each of USP Carbamazepine RS and USP Carbamazepine Related Compound A RS in Diluent

Standard solution: 0.1 mg/mL of USP Carbamazepine RS in Diluent

Sample solution: Nominally 0.1 mg/mL of carbamazepine from a volume of Oral Suspension prepared as follows. Weigh and transfer freshly mixed Oral Suspension equivalent to 20 mg of carbamazepine to a 200-mL volumetric flask. Add about 140 mL of Diluent, shake by mechanical means for about 30 min, sonicate for about 2 min, and dilute with Diluent to volume. Pass through a suitable filter of 0.2-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, 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

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 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) in the portion of Oral Suspension taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements for oral suspension packaged in single-unit containers

Deliverable Volume 〈698〉: Meets the requirements for oral suspension packaged in multiple-unit containers

5 IMPURITIES

Organic Impurities

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

Standard solution: 0.002 mg/mL each of USP Carbamazepine RS, USP Carbamazepine Related Compound A RS, and USP Carbamazepine

Related Compound B RS in Diluent

Sample solution: Nominally 1.0 mg/mL of carbamazepine from a volume of Oral Suspension prepared as follows. Weigh and transfer freshly mixed Oral Suspension equivalent to 50 mg of carbamazepine to a 50-mL volumetric flask. Add about 35 mL of Diluent, shake by mechanical means for about 30 min, sonicate for about 2 min, dilute with Diluent to volume, and shake for about 5 min. 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 carbamazepine related compound B in the portion of Oral Suspension taken:

Result = (r_U/r_S) x (C_S/C_U ) × 100

r_U = peak response of carbamazepine related compound B from the Sample solution

r_S = peak response of carbamazepine related compound B from the Standard solution

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

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

Calculate the percentage of each individual unspecified impurity in the portion of Oral Suspension taken:

Result = (r_U/r_S) x (C_S/C_U ) × 100

r_U = peak response of each 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 = nominal concentration of carbamazepine in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard any impurity peaks less than 0.05%.

Table 2

^a 10,11-Dihydrocarbamazepine.

^b Process impurity included in the table for identification only. Process impurities are controlled in the drug substance, and are not to be reported or included in the total impurities for the drug product.

^c 5H-Dibenz[b,f]azepine.

6 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total bacterial count does not exceed 1 × 10² cfu/g, and the tests for Salmonella species and Escherichia coli are negative.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers, protected from freezing and from excessive heat.

USP Reference Standards 〈11〉

USP Carbamazepine RS

USP Carbamazepine Related Compound A RS

10,11-Dihydrocarbamazepine.

C₁₅H₁₄N₂O 238.28

USP Carbamazepine Related Compound B RS

5H-Dibenz[b,f]azepine.

C₁₄H₁₁N 193.24