Oxcarbazepine Tablets

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Oxcarbazepine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂).

2 IDENTIFICATION

Change to read:

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1-May-2021)

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:

3.1 PROCEDURE

Buffer: 6.8 g/L of monobasic potassium phosphate in water. Add 2 mL of triethylamine. Adjust with phosphoric acid to a pH of 6.0.

Diluent: Methanol and water (80:20)

Mobile phase: Methanol, acetonitrile, and Buffer (22:16:62)

Standard stock solution: 0.5 mg/mL of USP Oxcarbazepine RS in Diluent. Sonication may be used to aid in dissolution.

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

Sample stock solution: Nominally equivalent to 1.2 mg/mL of oxcarbazepine from a portion of finely powdered Tablets (NLT 20), prepared as follows. Transfer a weighed quantity of powdered Tablets, equivalent to 600 mg of oxcarbazepine, to a 500-mL volumetric flask. Add Diluent to fill 50% of the final volume. Sonicate for 15 min with intermittent swirling, cool to room temperature, and dilute with Diluent to volume. Pass this solution through a suitable glass filter of 2-µm pore size, and discard the first portion of the filtrate.

Sample solution: Nominally (USP 1-May-2021) 0.1 mg/mL of oxcarbazepine in Mobile phase from a portion of the filtrate obtained from the Sample stock solution

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm. For Identification A, use a diode array detector in the range of 210-400 nm. (USP 1-May-2021)

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

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Temperatures

Sample: 5°

Column: 50°

Run time: NLT 1.6 times the retention time of oxcarbazepine (USP 1-May-2021)

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0% (USP 1-May-2021)

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) in the portion of Tablets 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 = nominal concentration of oxcarbazepine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

4.1.1 Test 1

Medium

For Tablets labeled to contain 150 mg: 0.3% (w/v) sodium dodecyl sulfate in water, 900 mL, deaerated

For Tablets labeled to contain 300 mg: 0.6% (w/v) sodium dodecyl sulfate in water, 900 mL, deaerated

For Tablets labeled to contain 600 mg: 1.0% (w/v) sodium dodecyl sulfate in water, 900 mL, deaerated

Apparatus 2: 60 rpm

Times: 30 and 60 min

Standard stock solution: 0.35 mg/mL of USP Oxcarbazepine RS in methanol

Standard solution: Dilute the Standard stock solution with the corresponding Medium to obtain a final concentration of 0.0175 mg/mL of USP Oxcarbazepine RS.

Sample solution: Use portions of the solution under test passed through a suitable filter of 0.45-µm pore size. The volume of the solution under test withdrawn must be replaced by the same volume of corresponding Medium. Dilute with the appropriate Medium if necessary, according to the Tablet strength, to obtain a final concentration similar to that of the Standard solution.

Instrumental conditions

Mode: UV-Vis

Analytical wavelength: 256 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) dissolved at 30 min (Q₃₀):

Q₃₀ = (A_U/A_S) x (C_S/L) x D x V x 100

Calculate the percentage of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) dissolved at 60 min (Q₆₀):

Q₆₀ = [(A_U/A_S) x (C_S/L) x D x V x 100] + [Q₃₀ x (V_S/V)]

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

D = dilution factor of the Sample solution

V = volume of Medium, 900 mL

V_S = volume of the solution under test withdrawn (mL)

Tolerances: NLT 70% (Q) of the labeled amount of oxcarbazepine is dissolved in 30 min; NLT 80% (Q) of the labeled amount of oxcarbazepine is dissolved in 60 min.

4.1.2 Test 2: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.

Medium

For Tablets labeled to contain 150 mg: 0.3% (w/v) sodium dodecyl sulfate in water; 900 mL, deaerated

For Tablets labeled to contain 300 mg: 0.6% (w/v) sodium dodecyl sulfate in water, 900 mL, deaerated

For Tablets labeled to contain 600 mg: 1.0% (w/v) sodium dodecyl sulfate in water, 900 mL, deaerated

Apparatus 2: 60 rpm

Times: 30 and 60 min

Standard stock solution: 3.3 mg/mL of USP Oxcarbazepine RS in methanol. [NOTE-This solution is stable for 22 h at 10°.]

Standard solution: Dilute the Standard stock solution with the corresponding Medium, according to the Tablet strength, to obtain a final concentration of (L/900) mg/mL, where L is the label claim in mg/Tablet.

Sample solution: Use portions of the solution under test passed through a suitable filter of 0.45-µm pore size. The volume of the solution under test withdrawn must be replaced by the same volume of corresponding Medium.

Instrumental conditions

Mode: UV-Vis

Analytical wavelength: 304 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) dissolved at 30 min (Q₃₀):

Q₃₀ = (A_U/A_S) x (C_S/L) x D x V x 100

Calculate the percentage of the labeled amount of oxcarbazepine (C₁₅H₁₂N₂O₂) dissolved at 60 min (Q₆₀):

Q₆₀ = [(A_U/A_S) x (C_S/L) x D x V x 100] + [Q₃₀ x (V_S/V)]

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

D = dilution factor of the Sample solution

V = volume of Medium, 900 mL

V_S = volume of the solution under test withdrawn (mL)

Tolerances

For Tablets labeled to contain 150 or 300 mg: NLT 70% (Q) of the labeled amount of oxcarbazepine is dissolved in 30 min; NLT 80% (Q) of the labeled amount of oxcarbazepine is dissolved in 60 min.

For Tablets labeled to contain 600 mg: NLT 50% (Q) of the labeled amount of oxcarbazepine is dissolved in 30 min; NLT 80% (Q) of the labeled amount of oxcarbazepine is dissolved in 60 min.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

[NOTE-On the basis of the synthetic route, perform either Organic Impurities, Procedure 1 or Organic Impurities, Procedure 2. If methoxycarbamazepine is a potential degradation product, Procedure 1 is recommended. If carbamazepinedione or dibenzazepinodione is a potential degradation product, Procedure 2 is recommended.]

Change to read:

5.1 ORGANIC IMPURITIES, PROCEDURE 1

Buffer: Prepare as directed in the Assay.

Diluent: Methanol and water (60:40)

Mobile phase: Methanol, acetonitrile, and Buffer (29:21:75)

System suitability solution: 0.5 mg/mL of USP Oxcarbazepine RS and 1.0 µg/mL of USP Carbamazepine RS in Mobile phase

Standard solution: 0.5 µg/mL of USP Oxcarbazepine RS in Mobile phase

Sample stock solution: Nominally equivalent to 1.2 mg/mL of oxcarbazepine from a portion of finely powdered Tablets (NLT 20), prepared as follows. Transfer a weighed quantity of powdered Tablets, equivalent to 600 mg of oxcarbazepine, to a 500-mL volumetric flask. Add Diluent to fill 50% of the final volume. Sonicate for 15 min with intermittent swirling, cool to room temperature, and dilute with Diluent to volume. Pass this solution through a suitable glass filter of 2-um pore size, and discard the first portion of the filtrate.

Sample solution: Nominally 500 µg/mL (USP 1-May-2021) of oxcarbazepine from the Sample stock solution in Mobile phase

Chromatographic system: Proceed as directed in the Assay, except for the Run time.

Run time: NLT 10 times the retention time of oxcarbazepine (USP 1-May-2021)

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for relative retention times.]

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 any individual degradation product in the portion of Tablets taken:

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

r_U = peak response of each individual degradation product (USP 1-May-2021) 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 (µg/mL) (USP 1-May-2021)

C_U = nominal concentration of oxcarbazepine in the Sample solution (µg/mL) (USP 1-May-2021)

F = relative response factor for the corresponding degradation product (USP 1-May-2021) (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a 10(11H)-Oxo-5H-dibenz[b,f]azepine.

^b 10-Methoxy-5H-dibenz[b,f]azepine-5-carboxamide.

Change to read:

5.2 ORGANIC IMPURITIES, PROCEDURE 2

Buffer A: 4.2 g of tris(hydroxymethyl)amino methane and 0.2 g of edetate disodium in 1 L of water

Buffer B: 18 g of tris(hydroxymethyl)amino methane and 0.9 g of edetate disodium in 1 L of water

Diluent: Acetonitrile and 1.8 g/L of ascorbic acid in water (1:99)

Solution A: Acetonitrile, tetrahydrofuran, and Buffer A (5:10:85)

Solution B: Acetonitrile, tetrahydrofuran, and Buffer B (70:10:20)

Mobile phase: See Table 2.

Table 2

System suitability stock solution: 1 µg/mL of USP Oxcarbazepine Related Compound C RS and 12 µg/mL of USP Carbamazepine RS in acetonitrile. Sonication may be used to aid in dissolution. [NOTE-The water bath temperature should not exceed 23°.]

(USP 1-System suitability solution: 0.05 µg/mL of USP Oxcarbazepine Related Compound C RS and 0.6 µg/mL of USP Carbamazepine RS May-2021) prepared as follows. Transfer a suitable volume of System suitability stock solution to a volumetric flask containing 50% of the final volume of Diluent. Allow the solution to reach ambient temperature, and dilute with acetonitrile to volume.

Standard stock solution: 12 µg/mL of USP Carbamazepine RS in acetonitrile. Sonication may be used to aid in dissolution. [NOTE-The water bath temperature should not exceed 23°.]

Standard solution: 0.6 µg/mL of USP Carbamazepine RS from Standard stock solution prepared as follows. Transfer a suitable volume of Standard stock solution to a flask containing 50% of the final volume of Diluent and 20% of the final volume of acetonitrile. Allow the solution to reach ambient temperature, and dilute with acetonitrile to volume.

Sample stock solution: Nominally equivalent to (USP 1-May-2021) 1.5 mg/mL of oxcarbazepine from a portion of finely powdered Tablets (NLT 20) prepared as follows. Transfer a weighed quantity of powdered Tablets, equivalent to about 375 mg of oxcarbazepine, to a 250-mL volumetric flask. Add 150 mL of acetonitrile, and sonicate for 15 min. Shake for 15 min, and dilute with acetonitrile to volume. Mix, and allow the suspension to settle for 30 min. Use the supernatant. [NOTE-The water bath temperature should not exceed 23°.]

Sample solution: Nominally 300 µg/mL (USP 1-May-2021) of oxcarbazepine from the Sample stock solution prepared as follows. Transfer a suitable volume of Sample stock solution to a volumetric flask containing 50% of the final volume of Diluent and 20% of the final volume of acetonitrile. Allow the solution to warm to ambient temperature, and dilute with acetonitrile to volume. Pass a portion of the solution through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.0-mm × 25-cm; 5-µm packing L1

Flow rate: 0.5 mL/min

Injection volume: 20 µL

Temperatures

Sample: 5°

Column: 35°

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 3 for relative retention times.]

Suitability requirements

Resolution: NLT 1.2 between oxcarbazepine related compound C and carbamazepine, System suitability solution

Relative standard deviation: NMT 15%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual degradation product in the portion of Tablets taken:

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

r_U = peak response of each individual degradation product (USP 1-May-2021) 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 (µg/mL) (USP 1-May-2021)

C_U = nominal concentration of oxcarbazepine in the Sample solution (µg/mL) (USP 1-May-2021)

F = relative response factor for the corresponding degradation product (USP 1-May-2021) (see Table 3)

Acceptance criteria: See Table 3.

Table 3

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

^b For system suitability and identification purposes only. Process impurity, not included in total.

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

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

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

6.2 LABELING

When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used. 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 Carbamazepine RS

USP Oxcarbazepine RS

USP Oxcarbazepine Related Compound C RS

Acridin-9(10H)-one.

C₁₃H₉NO 195.22