Carbamazepine Extended-Release Tablets

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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To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click www.uspnf.com/rb-carbamazepine-ert-20240628.

1 DEFINITION

Carbamazepine Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of carbamazepine (C₁₅H₁₂N₂O).

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Standard solution: 10 μg/mL of USP Carbamazepine RS in methanol

Sample solution: Finely powder 1 Tablet, and quantitatively transfer the powder, with the aid of methanol, to a 100-mL volumetric flask. Add about 70 mL of methanol, and shake by mechanical means for 60 min. Sonicate for 15 min, and dilute with methanol to volume. Allow to stand for 10–15 min. Dilute a portion of the clear solution with methanol to obtain a solution containing about 10 μg/mL of carbamazepine. Acceptance criteria: Meet 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

Mobile phase: Methanol, methylene chloride, and water (450:45:600)

Internal standard solution: 600 μg/mL of Phenytoin in methanol

Standard stock solution: 200 μg/mL of USP Carbamazepine RS in methanol

Standard solution: 100 μg/mL of carbamazepine from Standard stock solution in Internal standard solution

System suitability solution: 50 μg/mL of carbamazepine from Standard solution in Internal standard solution

Sample stock solution A: Nominally 4 mg/mL of carbamazepine from finely powdered Tablets prepared as follows. Finely powder 10 Tablets.

Transfer the powder to an appropriate volumetric flask with the aid of methanol. Add 70% of the flask volume of methanol. Shake by mechanical means for 60 min. Sonicate for 15 min, and dilute with methanol to volume. Allow to stand for 10–15 min, and then filter a portion of the supernatant. Use the clear filtrate.

Sample stock solution B: Nominally 0.2 mg/mL of carbamazepine from Sample stock solution A in methanol

Sample solution: Nominally 100 μg/mL of carbamazepine from Sample stock solution B in Internal standard solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Columns

Guard: 4.6-mm × 30-mm; 7-μm packing L7

Analytical: 3.9-mm × 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 10 μL

System suitability

Sample: System suitability solution

[Note—The relative retention times for phenytoin and carbamazepine are about 0.8 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.8 between phenytoin and carbamazepine

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

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

Result = (R_U/R_S ) × (C_S/C_U) × 100

R_u = peak response ratio of carbamazepine to the internal standard from the Sample solution

R_s = peak response ratio of carbamazepine to the internal standard from the Standard solution

C_s = concentration of USP Carbamazepine RS in the Standard solution (μg/mL)

C_u= nominal concentration of carbamazepine in the Sample solution (μg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Test 1

Medium

For Tablets labeled to contain 100 mg or 200 mg: Water; 900 mL

For Tablets labeled to contain 400 mg: Water; 1800 mL

Apparatus 1: 100 rpm

Times: 3, 6, 12, and 24 h

Standard solution: USP Carbamazepine RS in Medium

Sample solution: Filtered portions of the solution under test, diluted with Medium if necessary

Instrumental conditions

Mode: UV

Analytical wavelength: The wavelength of maximum absorbance at about 284 nm

Analysis

Samples: Standard solution and Sample solution

Determine the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at each time using the UV absorption.

Tolerances: See Table 1.

Table 1

The percentages of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at the times specified conform to Dissolution 〈711〉,

Acceptance Table 2.

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

Medium

For Tablets labeled to contain 100 or 200 mg: Water; 900 mL

For Tablets labeled to contain 400 mg: Water; 1800 mL

Apparatus 2: 100 rpm, with sinkers

Times: 2, 4, 12, and 24 h

Standard stock solution: 0.55 mg/mL of USP Carbamazepine RS in methanol. Sonication may be used to promote dissolution.

Standard solution: 0.0088 mg/mL of USP Carbamazepine RS from Standard stock solution in Medium

Sample stock solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. Discard the first 3 mL of the filltrate. Replace the portion removed from the solution under test with the same volume of Medium.

Sample solution

For Tablets labeled to contain 100 mg: Transfer 2.0 mL of Sample stock solution to a 25-mL volumetric flask and dilute with Medium to volume.

For Tablets labeled to contain 200 or 400 mg: Transfer 2.0 mL of Sample stock solution to a 50-mL volumetric flask and dilute with Medium to volume.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 284 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C ) of carbamazepine (C₁₅H₁₂N₂O) in the sample withdrawn from the vessel at each time point (i):

Result = (A_U /A_S ) × C_S x D

A_U = absorbance from the Sample solution at time point i

A_S = absorbance from the Standard solution

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

D = dilution factor for the Sample solution

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at each time point (i):

Result₁ = C₁ x V x (1/L) x 100

Result₂ = [(C₂xV₂) + (C₁xV_S) x (1/L) x 100

Result₃ = {(C₃ × V) + [(C₁ + C₂ ) × V_S]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₁ + C₂ + C₃ ) × V_S]} × (1/L) × 100

C_i = concentration of carbamazepine in the portion of the sample withdrawn at time point i (mg/mL)

V = volume of Medium, 900 or 1800 mL

L = label claim (mg/Tablet)

V_s = volume of the Sample solution withdrawn at each time point and replaced with Medium (mL)

Tolerances: See Table 2.

The percentages of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at the times specified conform to Dissolution 〈711〉,

Acceptance Table 2.

Table 2

Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: 5 g/L of sodium dodecyl sulfate in water; 900 mL, deaerated if necessary

Apparatus 1: 100 rpm, with a fixture made of 316 stainless steel to prevent the Tablets from turning during the test (see Figure 1).

For Tablets with a release hole, orient the hole facing downward in the basket.

Times: 3, 6, 12, and 24 h

Standard stock solution: 0.22 mg/mL of USP Carbamazepine RS prepared as follows. Weigh a suitable amount of USP Carbamazepine RS in a suitable volumetric flask. Add methanol to 10% of the flask volume and shake for 10 min to dissolve. Dilute with water to volume.

Standard solution: 0.0088 mg/mL of USP Carbamazepine RS from Standard stock solution in Medium

Sample solution: At the specified time points, withdraw a suitable volume of the solution under test. Pass through a suitable filter of 0.45- μm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained. Dilute with Medium to a concentration similar to that of the Standard solution.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 284 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C ) of carbamazepine (C₁₅H₁₂N₂O) in the sample withdrawn from the vessel at each time point (i):

Result = (A _U/A_S ) × C_S × D

A_U = absorbance from the Sample solution at time point i

A_S = absorbance from the Standard solution

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

D = dilution factor for the Sample solution

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V − V_S)] + (C₁ × V_S)} × (1/L) × 100

Result₃ = ({C₃ × [V − (2 × V_S)]} + [(C₂ + C₁ ) × V_S ]) × (1/L) × 100

Result₄ = ({C₄ × [V − (3 × V_S)]} + [(C₃ + C₂ + C₁ ) × V_S]) × (1/L) × 100

C_i = concentration of carbamazepine in the portion of the sample withdrawn at time point i (mg/mL)

V = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point from the Medium (mL)

Tolerances: See Table 3.

Table 3

The percentages of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at the times specified conform to Dissolution 〈711〉,

Acceptance Table 2.

Test 4: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.

Medium

For Tablets labeled to contain 100 or 200 mg: Water; 900 mL

For Tablets labeled to contain 400 mg: Water; 1800 mL

Apparatus 1: 100 rpm

For Tablets with a release hole, orient the hole facing downward in the basket.

Times: 3, 6, 12, and 24 h

Standard stock solution: 0.22 mg/mL of USP Carbamazepine RS prepared as follows. Transfer a suitable amount of USP Carbamazepine

RS to a suitable volumetric flask. Add methanol to 5% of the ask volume. Sonicate to dissolve. Dilute with Medium to volume.

Standard solution: 0.011 mg/mL of USP Carbamazepine RS from Standard stock solution in Medium

Sample stock solution: At the specified time points, withdraw a suitable volume of the solution under test. Pass through a suitable filter of

0.45-μm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained. Replace the portion removed from the solution under test with the same volume of Medium.

Sample solution

For Tablets labeled to contain 100 mg: Dilute 5 mL of Sample stock solution to 50 mL with Medium.

For Tablets labeled to contain 200 or 400 mg: Dilute 5 mL of Sample stock solution to 100 mL with Medium.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 284 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C ) of carbamazepine (C₁₅H₁₂N₂O) in the sample withdrawn from the vessel at each time point (i):

Result_i = (A_U/A_S) × C_S × D

A_U = absorbance from the Sample solution at time point i

A_S = absorbance from the Standard solution

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

D = dilution factor for the Sample solution

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at each time point (i):

Result₁ = C₁ x V x (1/L) x 100

Result₂ = [(C₂xV₂) + (C₁xV_S) x (1/L) x 100

Result₃ = {(C₃ × V) + [(C₁ + C₂ ) × V_S]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₁ + C₂ + C₃ ) × V_S]} × (1/L) × 100

C_i = concentration of carbamazepine in the portion of the sample withdrawn at time point i (mg/mL)

V = volume of Medium, 900 or 1800 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point and replaced with Medium (mL)

Tolerances: See Table 4.

Table 4

The percentages of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at the times specified conform to Dissolution 〈711〉,

Acceptance Table 2.

Test 5: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.

Medium

For Tablets labeled to contain 100 or 200 mg: Water; 900 mL, deaerated

For Tablets labeled to contain 400 mg: Water; 1800 mL, deaerated

Apparatus 1: 10-mesh basket, 100 rpm

Use a suitable sinker1 for Tablets labeled to contain 100 or 200 mg. For Tablets with a release hole, orient the hole facing downward in the basket.

Times: 3, 6, 12, and 24 h

Standard solution

For Tablets labeled to contain 100 mg: 0.11 mg/mL of USP Carbamazepine RS prepared as follows. Transfer a suitable amount of USP

Carbamazepine RS to a suitable volumetric flask. Add methanol to 2.5% of the flask volume. Sonicate to dissolve. Dilute with Medium to volume.

For Tablets labeled to contain 200 or 400 mg: 0.22 mg/mL of USP Carbamazepine RS prepared as follows. Transfer a suitable amount of

USP Carbamazepine RS to a suitable volumetric flask. Add methanol to 5% of the flask volume. Sonicate to dissolve. Dilute with Medium to volume.

Sample solution: At the speci

ed time points, withdraw a suitable volume of the solution under test. Pass through a suitable filter of 0.45- μm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 284 nm

Cell

For Tablets labeled to contain 100 mg: 0.2 cm

For Tablets labeled to contain 200 or 400 mg: 0.1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C ) of carbamazepine (C₁₅H₁₂N₂O) in the sample withdrawn from the vessel at each time point (i):

Result_i = (A_u/A_s ) × C_s

A_U = absorbance from the Sample solution at time point i

A_s = absorbance from the Standard solution

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

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V − V_S)] + (C₁ × V_S)} × (1/L) × 100

Result₃ = ({C₃ × [V − (2 × V_S)]} + [(C₂ + C₁ ) × V_S ]) × (1/L) × 100

Result₄ = ({C₄ × [V − (3 × V_S)]} + [(C₃ + C₂ + C₁ ) × V_S]) × (1/L) × 100

C_i = concentration of carbamazepine in the portion of the sample withdrawn at time point i (mg/mL)

V = volume of Medium, 900 or 1800 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point from the Medium (mL)

Tolerances: See Table 5.

Table 5

The percentages of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at the times speciFIed conform to Dissolution 〈711〉,

Acceptance Table 2.

Test 6: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6.

Medium

For Tablets labeled to contain 100 or 200 mg: Water; 900 mL, deaerated

For Tablets labeled to contain 400 mg: Water; 1800 mL, deaerated

Apparatus 2: 75 rpm

Times: 1, 3, 8, and 24 h

Solution A: Dilute 0.1 mL of phosphoric acid with water to 10 mL

Solution B: 1000 mL of water. Adjust with Solution A to a pH of 3.5.

Mobile phase: Methanol and Solution B (80:20)

Standard stock solution: 0.22 mg/mL of USP Carbamazepine RS prepared as follows. Transfer a suitable amount of USP Carbamazepine

RS to a suitable volumetric flask. Add methanol to 5% of the flask volume. Sonicate to dissolve. Dilute with Medium to volume.

Standard solution

For Tablets labeled to contain 100 mg: 0.11 mg/mL of USP Carbamazepine RS from the Standard stock solution in Medium

For Tablets labeled to contain 200 or 400 mg: 0.22 mg/mL of USP Carbamazepine RS from the Standard stock solution without dilution

Sample solution: At the specified time points, withdraw a suitable volume of the solution under test. Pass through a suitable filter of 0.45-μm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained. Replace the portion removed from the solution under test with the same volume of Medium.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 285 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 5 μL

Run time: NLT 2 times the retention time of carbamazepine

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C ) of carbamazepine (C₁₅H₁₂N₂O) in the sample withdrawn from the vessel at each time point (i):

Result_i = (r_u/r_s ) × C_s

r_u = peak response of carbamazepine 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)

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at each time point (i):

Result₁ = C₁ x V x (1/L) x 100

Result₂ = [(C₂xV₂) + (C₁xV_S) x (1/L) x 100

Result₃ = {(C₃ × V) + [(C₁ + C₂ ) × V_S]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₁ + C₂ + C₃ ) × V_S]} × (1/L) × 100

C_i = concentration of carbamazepine in the portion of the sample withdrawn at time point i (mg/mL)

V = volume of Medium, 900 or 1800 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point and replaced with Medium (mL)

Tolerances: See Table 6.

Table 6

The percentages of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at the times specified conform to Dissolution 〈711〉,

Acceptance Table 2.

Test 7: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 7.

Medium

For Tablets labeled to contain 100 or 200 mg: Water; 900 mL, deaerated

For Tablets labeled to contain 400 mg: Water; 1800 mL, deaerated

Apparatus 1: 100 rpm with sinker. [Note—A suitable 8-mesh basket sinker with cover may be used.]

For Tablets with a release hole, orient the hole facing downward in the basket.

Times

For Tablets labeled to contain 100 mg: 2, 4, 6, 12, and 24 h

For Tablets labeled to contain 200 or 400 mg: 2, 4, 6, and 24 h

Mobile phase: Methanol, water, triethylamine, and trifluoroacetic acid (60: 40: 0.1: 0.1)

Standard solution: 0.22 mg/mL of USP Carbamazepine RS prepared as follows. Weigh a suitable amount of USP Carbamazepine RS in a suitable volumetric flask. Add methanol to 5% of the flask volume and sonicate to dissolve. Dilute with Medium to volume.

Sample solution: At the specified time points, withdraw a suitable volume of the solution under test. Pass through a suitable filter of 0.45-μm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 285 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 2 times the retention time of carbamazepine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C ) of carbamazepine (C₁₅H₁₂N₂O) in the sample withdrawn from the vessel at each time point (i):

Result_i = (r_u/r_s ) × C_s

r_u = peak response of carbamazepine from the Sample solution

r_s = peak response of carbamazepine from the Standard solution

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

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V − V_S)] + (C₁ × V_S)} × (1/L) × 100

Result₃ = ({C₃ × [V − (2 × V_S)]} + [(C₂ + C₁ ) × V_S ]) × (1/L) × 100

Result₄ = ({C₄ × [V − (3 × V_S)]} + [(C₃ + C₂ + C₁ ) × V_S]) × (1/L) × 100

Result₅ = ({C₅ × [V − (4 × V_s)]} + [(C₄ + C₃ + C₂ + C₁ ) × V_s]) × (1/L) × 100

C_i = concentration of carbamazepine in the portion of the sample withdrawn at time point i (mg/mL)

V = volume of Medium, 900 or 1800 mL

L = label claim (mg/Tablet)

V_s = volume of the Sample solution withdrawn at each time point from the Medium (mL)

Tolerances: See Table 7 and Table 8.

Table 7

Table 8

The percentages of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at the times specified conform to Dissolution 〈711〉,

Acceptance Table 2.

Test 10: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 10.

Medium

For Tablets labeled to contain 100 or 200 mg: Water; 900 mL, deaerated, if necessary

For Tablets labeled to contain 400 mg: Water; 1800 mL, deaerated, if necessary

Apparatus 1: 10-mesh basket, 100 rpm

Use a suitable sinker.2

For Tablets with a release hole, orient the hole facing downward in the basket.

Times: 2, 4, 8, and 20 h

Solution A: Dilute 10 mL of phosphoric acid with water to 100 mL.

Buffer: Dissolve 1.36 g of potassium phosphate, monobasic in 1000 mL of water. Add 2 mL of triethylamine. Adjust with Solution A to a pH of 6.0.

Mobile phase: Acetonitrile, methanol, and Buffer (20:22:58)

Diluent: Methanol and water (80:20)

Standard stock solution: 1.12 mg/mL of USP Carbamazepine RS in Diluent. Sonicate to dissolve, if necessary.

Standard solution

For Tablets labeled to contain 100 mg: 0.112 mg/mL of USP Carbamazepine RS from the Standard stock solution in Medium

For Tablets labeled to contain 200 or 400 mg: 0.224 mg/mL of USP Carbamazepine RS from the Standard stock solution in Medium

Sample solution: At the specified time points, withdraw a suitable volume of the solution under test. Pass through a suitable filter of 0.45-μm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained. Replace the portion removed from the solution under test with the same volume of Medium.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 305 nm

Column: 4.6-mm × 15-cm; 5-μm packing L7

Column temperature: 50°

Flow rate: 1.5 mL/min

Injection volume: 5 μL

Run time: NLT 1.9 times the retention time of carbamazepine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C ) of carbamazepine (C₁₅H₁₂N₂O) in the sample withdrawn from the vessel at each time point (i):

Result = (r_S/r_U) × C_S

r_U = peak response of carbamazepine 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)

Calculate the percentage of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at each time point (i):

Result₁ = C₁ x V x (1/L) x 100

Result₂ = [(C₂xV₂) + (C₁xV_S) x (1/L) x 100

Result₃ = {(C₃ × V) + [(C₁ + C₂ ) × V_S]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₁ + C₂ + C₃ ) × V_S]} × (1/L) × 100

C_i = concentration of carbamazepine in the portion of the sample withdrawn at time point i (mg/mL)

V = volume of Medium, 900 or 1800 mL

L = label claim (mg/Tablet)

V_s = volume of the Sample solution withdrawn at each time point and replaced with Medium (mL)

Tolerances: See Table 9.

Table 9

The percentages of the labeled amount of carbamazepine (C₁₅H₁₂N₂O) dissolved at the times specified conform to Dissolution 〈711〉,

Acceptance Table 2. (RB 1-Jul-2024)

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities: Procedure 1

Mobile phase: Methanol, methylene chloride, and water (450:45:600)

System suitability solution: 60 μg/mL of phenytoin and 20 μg/mL of USP Carbamazepine RS in methanol

Standard solution: 4 μg/mL of USP Carbamazepine RS in methanol

Sample solution: Use Sample stock solution A from the Assay.

Chromatographic system and System suitability: Proceed as directed in the Assay.

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) x (C_S/C_U ) × 100

r_U = peak response of each 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

Any individual unspecified degradation product: NMT 0.2%

Organic Impurities: Procedure 2

Mobile phase: Methanol, acetonitrile, and water (35:15:50)

System suitability solution: 12.5 μg/mL of iminostilbene and 5.0 μg/mL of USP Carbamazepine RS in methanol

Standard solution: 4 μg/mL of USP Carbamazepine RS in methanol

Sample solution: Use Sample stock solution A from the Assay.

Chromatographic system: Proceed as directed in the Assay.

System suitability

Sample: System suitability solution

[Note—The relative retention times for carbamazepine and iminostilbene are about 0.3 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 10.0 between carbamazepine and iminostilbene

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) x (C_S/C_U ) × 100

r_U = peak response of each 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

Any individual unspecified degradation product: NMT 0.2%

Total impurities: NMT 0.5% for all impurities from Procedure 1 and Procedure 2.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

Labeling: The labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Carbamazepine RS