Lamotrigine 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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1 DEFINITION

Lamotrigine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of lamotrigine (C₉H₇Cl₂N₅).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U (CN 1-May-2020)

Standard solution: 0.02 mg/mL of USP Lamotrigine RS in 0.01 N hydrochloric acid

Sample solution: 0.02 mg/mL of lamotrigine from crushed powdered Tablets in 0.01 N hydrochloric acid

Acceptance criteria: The spectra of the Standard solution and Sample solution exhibit maxima and minima at the same wavelengths.

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

3 ASSAY

Procedure

Buffer: 0.8 g/L of ammonium acetate. Adjust with glacial acetic acid to a pH of 4.5.

Mobile phase: Methanol and Buffer (60:40)

Standard solution: 0.05 mg/mL of USP Lamotrigine RS in Mobile phase

Sample solution: Transfer an amount equivalent to 100 mg of lamotrigine from a portion of crushed Tablets (NLT 20) to a suitable volumetric flask to obtain a nominal concentration of lamotrigine of 1.0 mg/mL. Dissolve in 70% of the flask volume of Mobile phase by sonicating for 20 min. Dilute with Mobile phase to volume. Centrifuge the solution. Quantitatively dilute a suitable volume of centrifugate with Mobile phase to obtain a nominal concentration of 0.05 mg/mL of lamotrigine.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

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

Flow rate: 1 mL/min

Injection size: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0 for lamotrigine

Relative standard deviation: NMT 2.0% for lamotrigine

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lamotrigine (C₉H₇Cl₂N₅) in the portion of Tablets 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 Lamotrigine RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Determine the amount of lamotrigine (C₉H₇Cl₂N₅) dissolved by using one of the following methods.

Spectrometric method

Standard stock solution: 0.15 mg/mL of USP Lamotrigine RS in Medium prepared as follows. Dissolve a suitable quantity in 5% of the flask volume of methanol, then dilute with Medium to volume.

Standard solution: Dilute the Standard stock solution with Medium to obtain a final concentration of 0.028 mg/mL.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. Dilute with Medium according to Table 1.

Table 1

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 267 nm

Blank: Medium

Analysis

Calculate the percentage of the labeled amount of lamotrigine (C₉H₇Cl₂N₅) dissolved:

Result = (A_U/A_S) × (C_S/L) × D ×V × 100

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

Chromatographic method

Buffer and Mobile phase: Prepare as directed in the Assay.

Standard stock solution: 0.5 mg/mL of USP Lamotrigine RS in Medium, prepared as follows. Dissolve a suitable quantity in 15% of the flask volume of methanol, then dilute with Medium to volume.

Standard solution: (L/1000) mg/mL of USP Lamotrigine RS from the Standard stock solution in Medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

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

Detector: UV 310 nm

Flow rate: 1 mL/min

Injection size: See Table 2.

Table 2

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0 for lamotrigine

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lamotrigine (C₉H₇Cl₂N₅) dissolved:

Result = (r_U/r_S) × (C_S/L) × V × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of lamotrigine is dissolved.

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

Medium, Apparatus, and Time: Proceed as directed for Test 1.

Analysis: Determine the amount of lamotrigine dissolved using either the Spectrometric method or Chromatographic method described in Test 1.

Tolerances: NLT 75% (Q) of the labeled amount of lamotrigine is dissolved.

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

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 15 min

Standard solution: (L/900) mg/mL of USP Lamotrigine RS in Medium, where L is the Tablet label claim in mg

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 270 nm Cell

For Tablets labeled to contain 100, 150, or 200 mg: 0.2-cm flow cell

For Tablets labeled to contain 25 mg: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lamotrigine (C₉H₇Cl₂N₅) dissolved:

Result = (A_U/A_S) × (C_S/L) × V × 100

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)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of lamotrigine is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Buffer: Prepare as directed in the Assay.

Mobile phase: Acetonitrile, methanol, and Buffer (10:30:60)

Diluent: Methanol and Buffer (60:40)

System suitability solution: 1 μg/mL of Lamotrigine Related Compound B RS and 0.4 mg/mL of USP Lamotrigine RS in Diluent

Standard solution: 1.0 μg/mL of USP Lamotrigine RS in Diluent

Sample solution: Transfer an amount equivalent to 100 mg of lamotrigine from a portion of crushed Tablets (NLT 20) to a suitable volumetric flask to obtain a nominal concentration of lamotrigine of about 0.4 mg/mL. Dissolve in 70% of the flask volume of Mobile phase by sonicating and shaking intermittently for 30 min. Dilute with Diluent to volume. Pass through a membrane filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

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

Flow rate: 1 mL/min

Injection size: 5 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between lamotrigine related compound B and lamotrigine, System suitability solution

Tailing factor: NMT 2.0 for lamotrigine, Standard solution

Relative standard deviation: NMT 10.0% for lamotrigine, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Tablets taken:

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

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of lamotrigine from the Standard solution

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

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

F = relative response factor for the corresponding impurity (see Table 3)

Acceptance criteria: See Table 3.

Table 3

^a 2,3-Dichlorobenzoic acid.

^b 3-Amino-6-(2,3-dichlorophenyl)-1,2,4-triazin-5(4H)-one.

ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.

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

USP Reference Standards 〈11〉

USP Lamotrigine RS

USP Lamotrigine Related Compound B RS

2,3-Dichlorobenzoic acid.

C₉H₇Cl₂N₂ 191.01