A Validated RP-HPLC-UV Method for Identification of Reference Standards of Degradation Products of Fenofibrate

Abstract

Background: During the stress degradation studies of Fenofibrate the structures of two major degradation products, namely 2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl propanoic acid and methyl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate, were characterized using LC-MS/MS studies under alkaline and acidic hydrolytic conditions, respectively. The present communication deals with synthesis, spectral characterization and further application of those reference standards of degradation products in identification of degradation products in bulk sample of drug through retention time matching studies. Methods: The reference standards of the degradation products were synthesized in the laboratory and their identity were confirmed using spectral studies. These were employed for retention matching studies using HPLC studies. The chromatographic conditions were as follows: stationary phase: Waters X Bridge C 18 column (250x4.6 mm, internal diameter, particle size 5 μm), mobile phase: acetonitrile: water in 75:25 v/v, column oven temperature: ambient, proportion. The chromatograms were monitored at 286 nm with a flowrate of 1 mL/min. The method was validated according to the ICH. guidelines. Results: Retention time values of synthesized reference standards were found to be identical with retention time values of those degradation products in stressed samples. The calibration curves showed good linear regression (r 2 >0.999) within test ranges. The method showed good reproducibility and sensitivity for quantification of both degradation products in samples. Method was precise and %recovery of both reference products was within 98-102%. Conclusion: This communication emphasizes use of non-compendial reference standards for quantification of degradation products by chromatographic methods. Quantitative validation parameters like Limit of detection and Limit of quantitation were established. Key words: Degradation impurities, Fenofibrate, Non-compendial reference standards, RP-HPLC, Retention time matching.