Oxcarbazepine

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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C₁₅H₁₂N₂O₂ 252.27

5H-Dibenz[b,f]azepine-5-carboxamide, 10,11-dihydro-10-oxo-;

10,11-Dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide CAS RN^®: 28721-07-5; UNII: VZI5B1W380.

1 DEFINITION

Oxcarbazepine contains NLT 98.0% and NMT 102.0% of oxcarbazepine (C₁₅H₁₂N₂O₂), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

[NOTE-If the spectrum obtained shows differences, dissolve the substance to be examined in chloroform, and evaporate to dryness. Compare the spectrum of the residue to that of a similarly prepared USP Oxcarbazepine RS.]

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

3.1 PROCEDURE

Buffer: 6.8 g/L of monobasic potassium phosphate in water. For each liter prepared, add 2 mL of triethylamine, and mix. Adjust with phosphoric acid to a pH of 6.0 ± 0.1.

Mobile phase: Methanol, acetonitrile, and Buffer (11:8:31)

Standard solution: 0.1 mg/mL of USP Oxcarbazepine RS in Mobile phase

Sample solution: 0.1 mg/mL of Oxcarbazepine in Mobile phase

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 50°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

3.3 System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of oxcarbazepine (C₁₅H₁₂N₂O₂) in the portion of Oxcarbazepine taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES, PROCEDURE 1

[NOTE-If oxcarbazepine related compound A and oxcarbazepine related compound B are known process impurities, Organic Impurities, Procedure 2 is recommended.]

Mobile phase: Prepare as directed in the Assay.

System suitability solution: 0.1 mg/mL each of USP Oxcarbazepine RS and USP Carbamazepine RS in Mobile phase

Standard solution: 0.25 µg/mL of USP Oxcarbazepine RS in Mobile phase

Sample solution: 0.5 mg/mL of Oxcarbazepine in Mobile phase

Chromatographic system: Proceed as directed in the Assay, except to use a run time 10 times the retention time of oxcarbazepine.

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 8.0 between oxcarbazepine and carbamazepine, System suitability solution

Relative standard deviation: NMT 10.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Oxcarbazepine taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of oxcarbazepine from the Standard solution

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

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

F relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

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

^b 10-Methoxy-5H-Dibenz(b,f]azepine-5-carboxamide.

^c 5H-Dibenz[b,f]azepine.

^d 10-Methoxy-5H-Dibenz[b,f]azepine.

4.3 ORGANIC IMPURITIES, PROCEDURE 2

Buffer A: 0.004 mol/L of monobasic potassium phosphate and 0.063 mol/L of dibasic sodium phosphate

Buffer B: To 1 L of 3.6 g/L edetate disodium in water add 1 L of Buffer A.

Diluent: 1.8 g/L of ascorbic acid in water

Solution A: Acetonitrile, tetrahydrofuran, Buffer B, and water (1:2:2:15)

Solution B: Acetonitrile, tetrahydrofuran, Buffer B, and water (6:1:1:2)

Mobile phase: See Table 2.

Table 2

System suitability solution: 2 µg/mL each of USP Oxcarbazepine Related Compound A RS, USP Oxcarbazepine Related Compound B RS, USP Oxcarbazepine Related Compound D RS, and USP Oxcarbazepine Related Compound E RS in a 1:1 mixture of acetonitrile and Diluent

Standard stock solution: 0.1 mg/mL of USP Oxcarbazepine RS in acetonitrile

Standard solution: 2 µg/mL of USP Oxcarbazepine RS in a 1:1 mixture of acetonitrile and Diluent

Sample solution: 1.0 mg/mL of Oxcarbazepine in a 1:1 mixture of acetonitrile and Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 25-cm; 3-µm packing L1

Column temperature: 50°

Flow rate: 0.8 mL/min

Injection volume: 50 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.0 between oxcarbazepine related compound A and oxcarbazepine related compound B; NLT 1.2 between oxcarbazepine related compound D and oxcarbazepine related compound E, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Oxcarbazepine taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of oxcarbazepine from the Standard solution

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

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

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3. [NOTE-Disregard any peak below 0.03%.]

Table 3

^a 10,11-Dioxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide.

^b N-Carbamoyl-10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide.

^c N-Formyl-10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide.

^d N-Acetyl-10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide.

^e 5H-Dibenzo[b,f]azepine-10,11-dione.

^f 10-(10-Oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamido)-5H-dibenzo[b,f]azepine-5-carboxamide.

5 SPECIFIC TESTS

WATER DETERMINATION, Method la (921): NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers. Store at controlled room temperature.

6.2 LABELING

If a test for Organic Impurities other than Procedure 1 is used, the labeling states the test with which the article complies.

6.3 USP REFERENCE STANDARDS (11)

USP Oxcarbazepine RS

USP Carbamazepine RS

USP Oxcarbazepine Related Compound A RS

N-Formyl-10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide.

C₁₆H₁₂N₂O₃ 280.28

USP Oxcarbazepine Related Compound B RS

N-Acetyl-10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide.

C₁₇H₁₄N₂O₃ 294.30

USP Oxcarbazepine Related Compound D RS

10-(10-Oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamido)-5H-dibenzo[b,f]azepine-5-carboxamide.

C₃₀H₂₂N₄O₃ 486.52

USP Oxcarbazepine Related Compound E RS

10(11H)-Oxo-5H-Dibenz[b,f]azepine.

C₁₄H₁₁NO 209.24