Lamotrigine Tablets for 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

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

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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

Buffer: 0.77 g/L of ammonium acetate in water; adjusted with glacial acetic acid to a pH of 4.5

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

Diluent: Acetonitrile, methanol, and Buffer (30:30:40)

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

Sample solution: Nominally 0.05 mg/mL of lamotrigine prepared as follows. Transfer NLT 6 Tablets for Oral Suspension to a suitable volumetric flask. Sonicate in 70% of the flask volume of Diluent for 30 min with intermittent shaking. Dilute with Diluent to final volume, and pass a portion through a suitable membrane filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm. For Identification A, use a diode array detector in the range of 200–400 nm.

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

Flow rate: 1.5 mL/min

Injection volume: 10 μL

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 percentage of the labeled amount of lamotrigine (C₉H₇Cl₂N₅) in the portion of Tablets for 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 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〉

Medium: 0.1 N hydrochloric acid; 900 mL, degassed

Apparatus 2: 50 rpm

Time: 15 min. [Note—The Sample solution may be analyzed using either Chromatographic procedure 1 or Chromatographic procedure 2.]

Standard stock solution: 0.5 mg/mL of USP Lamotrigine RS in methanol

Standard solution: (L/1000) mg/mL of USP Lamotrigine RS in Medium from the Standard stock solution, 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.

Determine the amount of lamotrigine dissolved by employing one of the following chromatographic procedures.

Chromatographic procedure 1

Buffer: To 1 L of 0.77 g/L of ammonium acetate in water add 2 mL of triethylamine, and adjust with glacial acetic acid to a pH of 7.5.

Mobile phase: Acetonitrile, methanol, and Buffer (20:15:65)

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 310 nm

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

Flow rate: 1 mL/min

Injection volume: 100 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Chromatographic procedure 2

Mobile phase: Acetonitrile, water, glacial acetic acid, and triethylamine (47:148:4:1). [Note—The Mobile phase is stable for 48 h at room temperature.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 270 nm

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

Flow rate: 1 mL/min

Injection volume: 10 μL

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 percentage of the labeled amount of lamotrigine dissolved:

Result = (r_U/r_S)x(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 USP Lamotrigine RS in the Standard solution (mg/mL)

L = label claim of lamotrigine (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

[Note—Procedure 1 is recommended if lamotrigine related compound B is a potential organic impurity. Procedure 2 is recommended if

lamotrigine related compound C is a potential organic impurity.]

Organic Impurities, Procedure 1

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

Standard solution: 0.8 μg/mL of USP Lamotrigine RS in Diluent

Sample solution: Nominally 0.25 mg/mL of lamotrigine prepared as follows. From NLT 20 Tablets for Oral Suspension ground to a fine powder, transfer an amount of powder to a suitable  flflask to obtain a nominal concentration of 0.25 mg/mL of lamotrigine in Diluent.

Sonicate for 15 min to dissolve the contents. Filter a portion, and discard the first 1 mL of the filtrate.

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 volume: 20 μL

System suitability

Sample: Standard solution

[Note—See Table 1 for relative retention times.]

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 10%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets for Oral Suspension taken:

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

r_U = peak response of each 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 each impurity (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a 2,3-Dichlorobenzoic acid.

Organic Impurities, Procedure 2 Mobile phase and Chromatographic system: Proceed as directed in Chromatographic procedure 2 in the Dissolution test.

Diluent: Methanol and water (40:60)

Standard solution: 0.2 mg/mL of USP Lamotrigine RS and 0.002 mg/mL of USP Lamotrigine Related Compound C RS prepared as follows.

Transfer suitable amounts of USP Lamotrigine RS and USP Lamotrigine Related Compound C RS to a suitable volumetric flflask. Add 40% of the flflask volume of methanol, and sonicate until dissolved. Allow to cool to room temperature, and dilute with water to volume.

Sample solution: Nominally 0.2 mg/mL of lamotrigine. Use 10 Tablets for Oral Suspension for a label claim of 25 mg or less and 5 Tablets for

Oral Suspension for a label claim of 50 mg or more prepared as follows. Transfer the appropriate number of Tablets for Oral Suspension to a suitable volumetric flflask. Add 40% of the flflask volume of water. Swirl until the tablets have disintegrated. Allow the effervescence to stop, and then add an additional 40% of the flflask volume of methanol. Sonicate the flflask for 10 min, and cool to room temperature. Dilute with water to volume. [Note—For Tablets for Oral Suspension with a 50 mg or higher label claim, a suitable intermediate concentration may be chosen. The final dilution to arrive at the nominal concentration is made using Diluent.]

System suitability

Sample: Standard solution

[Note—See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between lamotrigine and lamotrigine related compound C

Tailing factor: NMT 2.0 for lamotrigine and lamotrigine related compound C

Relative standard deviation: NMT 5.0% for lamotrigine related compound C and NMT 1.5% for lamotrigine

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of lamotrigine related compound C in the portion of Tablets for Oral Suspension taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of lamotrigine related compound C from the Sample solution

r_S = peak response of lamotrigine related compound C from the Standard solution

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

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

Calculate the percentage of any other individual unspecified impurity in the portion of Tablets for Oral Suspension taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of any other 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)

Acceptance criteria: See Table 2.

Table 2

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

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Store in tight, light-resistant containers, at controlled room temperature.

Labeling: If a procedure for Organic Impurities other than Procedure 1 is used, then the labeling states with which Organic Impurities procedure the article complies. The label states that the Tablets for Oral Suspension may be swallowed whole, chewed, or dispersed in water or diluted fruit juice.

USP Reference Standards 〈11〉

USP Lamotrigine RS

1,2,4-Triazine-3,5-diamine, 6-(2,3-dichlorophenyl).

C₉H₇Cl₂N₅ 256.09

USP Lamotrigine Related Compound C RS

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

C₉H₆Cl₂N₄O 257.08