Leflunomide 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

Leflunomide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of leflunomide (C₁₂H₉F₃N₂O₂).

2 IDENTIFICATION

Change to read:

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

Wavelength range: 220–360 nm

Sample solution: 0.01 mg/mL in methanol

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: Acetonitrile, triethylamine, and water (70:1:130). Adjust with phosphoric acid to a pH of 4.0.

System suitability solution A: 10 μg/mL of USP Leflunomide Related Compound A RS, 1 mg/mL of USP Leflunomide Related Compound B RS, and 100 μg/mL of USP Leflunomide Related Compound C RS in a minimum amount of acetonitrile, and diluted with Mobile phase

System suitability solution B: Transfer 100.0 mg of USP Leflunomide RS to a 100-mL volumetric flask. Dissolve in 2 mL of acetonitrile, add 1 mL of System suitability solution A and 80 mL of Mobile phase, and shake by mechanical means for 10 min. Dilute with Mobile phase to volume.

Standard solution: 1 mg/mL of USP Leflunomide RS in a minimum volume of acetonitrile, and diluted with Mobile phase

Sample solution: Transfer equivalent to 100 mg of leflunomide, from finely powdered Tablets (NLT 20), to a 100-mL volumetric flask. Add 20 mL of acetonitrile, dilute with Mobile phase to volume, and shake by mechanical means for 10 min. Pass through a membrane filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.0-mm × 12.5-cm; packing L1

Flow rate: 1 mL/min

Injection size: 10 μL

System suitability

Samples: System suitability solution B and Standard solution

[Note—The relative retention times for leflunomide related compound B, leflunomide related compound A, leflunomide related compound C, and leflunomide are 0.2, 0.4, 0.9, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between leflunomide related compound C and leflunomide, System suitability solution B

Tailing factor: NMT 3.0 for leflunomide, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of le

unomide (C₁₂H₉F₃N₂O₂) 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 Leflunomide RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium

For Tablets labeled to contain 10 or 20 mg: Water, 1000 mL, deaerated

For Tablets labeled to contain 100 mg: Water containing 0.6% of polyoxyethylene (23) lauryl ether; 1000 mL, deaerated

Apparatus 2: 100 rpm

Time: 30 min

Determine the amount of leflunomide (C₁₂H₉F₃N₂O₂) dissolved by using one of the following methods.

Spectrometric method

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 262 nm

Standard solution: USP Leflunomide RS in Medium. [Note—A volume of methanol not exceeding 2% of the final volume of the Standard solution may be used to dissolve leflunomide.]

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. Dilute with Medium to a concentration that is similar to that of the Standard solution, if necessary.

Chromatographic method

Mobile phase: Acetonitrile and water (1:1)

Standard solution: Transfer 22 mg of USP Leflunomide RS to a 100-mL volumetric flask. Add 40 mL of acetonitrile, and sonicate until dissolved. Add 40 mL of water, and cool to room temperature. Dilute with water to volume. Transfer 10.0 mL of this solution to a 100- mL volumetric flask, and dilute with water to volume.

Sample solution: Use portions of the solution under test passed through a suitable filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 260 nm

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

Flow rate: 1.5 mL/min

Injection size: 40 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 amount of leflunomide (C₁₂H₉F₃N₂O₂) 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 Leflunomide RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 1000 mL

Tolerances: NLT 80% (Q) of the labeled amount of leflunomide (C₁₂H₉F₃N₂O₂) is dissolved.

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

Medium, Apparatus 2, Time, Spectrometric method, and Chromatographic method: Proceed as directed for Test 1.

Tolerances: NLT 75% (Q) of the labeled amount of leflunomide (C₁₂H₉F₃N₂O₂) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

Procedure for content uniformity

Mobile phase, System suitability solution A, System suitability solution B, Standard solution, Chromatographic system, and

Analysis: Proceed as directed in the Assay.

Sample solution: Transfer 1 Tablet to a suitable volumetric flask, and prepare a solution having a concentration of 1 mg/mL of leflunomide.

Add Mobile phase 50% by volume, and shake to disintegrate the Tablet. After the Tablet is completely disintegrated, add acetonitrile 20% by volume, dilute with Mobile phase to volume, and shake again. Pass through a membrane filter.

5 IMPURITIES

5.1 Procedure

Mobile phase, System suitability solution A, System suitability solution B, Standard solution, Sample solution, and Chromatographic

system: Proceed as directed in the Assay.

5.2 Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_T) × 100

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

r_T = sum of all the peak responses of the related compounds and leflunomide from the Sample solution Acceptance criteria

Leflunomide related compound A: NMT 0.1%

Leflunomide related compound B: NMT 3.5%

Leflunomide related compound C: NMT 0.2%

Individual impurities: NMT 0.2%

Total impurities: NMT 4.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant, and humidity-resistant containers.

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 Leflunomide RS

USP Leflunomide Related Compound A RS

USP Leflunomide Related Compound B RS

USP Leflunomide Related Compound C RS