Leflunomide Tablets
DEFINITION
Leflunomide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of leflunomide (C12H9F3N2O2).
IDENTIFICATION
• A. Ultraviolet Absorption 
197U
197U
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.
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:
Equivalent to 100 mg of leflunomide from Tablets (finely powder NLT 20 Tablets), 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
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:
Standard solution and System suitability solution B
[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
Tailing factor:
NMT 3.0 for leflunomide
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C12H9F3N2O2 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Leflunomide RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of leflunomide in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
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 lauryl ether; 1000 mL, deaerated
Apparatus 2:
100 rpm
Time:
30 min
Determine the amount of C12H9F3N2O2 dissolved using one of the following methods.
Spectrometric method
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 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
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 C12H9F3N2O2 dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Leflunomide RS in the Standard solution (mg/mL) |
| L | = | = Tablet label claim (mg) |
| V | = | = volume of Medium (mL), 1000 |
Tolerances:
NLT 80% (Q) of the labeled amount of 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 C12H9F3N2O2 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
Procedure for content uniformity
Mobile phase, System suitability solutions, Standard solution, and Chromatographic system:
Prepare 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.
Analysis:
Proceed as directed in the Assay.
IMPURITIES
Organic Impurities
• Procedure
Mobile phase, System suitability solutions, Standard solution, Sample solution, and Chromatographic system:
Proceed as directed in the Assay.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each individual impurity in the portion of Tablets taken:
Result = (rU/rT) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rT | = | = 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%
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
11
USP Leflunomide RS 
') + '&img=../../images/v35300/cas-75706-12-6.gif',600,500);)
USP Leflunomide Related Compound A RS
USP Leflunomide Related Compound B RS
USP Leflunomide Related Compound C RS
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Clydewyn M. Anthony, Ph.D.
Senior Scientific Liaison 1-301-816-8139 |
(SM22010) Monographs - Small Molecules 2 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3646
Pharmacopeial Forum: Volume No. 37(3)