Abstract
The present paper deals with the development of stability indicating reversed phase high-performance liquid chromatographic (RP-HPLC) method for leflunomide, a disease-modifying antirheumatic drug in presence of its degradation products formed during forced decomposition studies. Forced degradation studies were performed on the bulk drug by using acid (0.1 N hydrochloric acid), base (0.1 N sodium hydroxide), water (neutral hydrolysis), 3% v/v hydrogen peroxide (oxidation), dry heat (60°C) and UV light (254 nm). Degradation was observed for leflunomide in acidic and basic media only and the formed degradation products were found to be 5-methylisoxazole-4-carboxylic acid (degradation product-1) and 4-(trifluoromethyl)-aniline (degradation product-2). Successful separation of the drug from the degradation products formed under different stress conditions was achieved on a Novapak C18 column (150 mm × 3.9 mm, 4 µm particle size) using methanol- phosphate buffer (pH 5.3; 20 mM) (7:3, v/v) as the mobile phase at a flow rate of 1 mL/min. The detection wavelength was 260 nm. The developed method was completely validated and proved to be robust. As the method could effectively separate the drug from its degradation products, it can be employed for analysis of the samples of stability study.
Highlights
The chemical name of leflunomide is N- (4 ́trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide (Kher et al, 2011), which is an isoxazole derivative and inhibitor of de novo pyrimidine synthesis (Katarzyna et al, 1998; Migita et al, 2005), represents a new class of disease modifying anti rheumatic drugs (Yadav et al, 2010)
The present paper deals with the development of stability indicating a reversed phase high-performance liquid chromatographic (RP-high performance liquid chromatographic (HPLC)) method for leflunomide, a disease-modifying antirheumatic drug in presence of its degradation products formed during forced decomposition studies
As the method could effectively separate the drug from its degradation products, it can be employed for analysis of the samples of stability study
Summary
The chemical name of leflunomide is N- (4 ́trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide (Kher et al, 2011), which is an isoxazole derivative and inhibitor of de novo pyrimidine synthesis (Katarzyna et al, 1998; Migita et al, 2005), represents a new class of disease modifying anti rheumatic drugs (Yadav et al, 2010). The stability assessment of any promising drug candidate plays a vital role in its preformulation study. Many environmental conditions such as heat, light, moisture as well as the inherent chemical susceptibility of a compound to hydrolysis or oxidation play an important role in pharmaceutical stability. The exposition of the drug substance to extreme external conditions helps to reveal and identify the likely degradation products which will open a new scope of research on toxicity study. The findings of toxicity study will help in the scrupulous determination of expiry, adverse effects etc
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