LC-MS/MS Studies for the identification and characterization of degradation products of fenofibrate and their degradation pathways

Abstract

In the present study, the degradation behavior of Fenofibrate under different International Conference on Harmonization (ICH) suggested conditions was studied. Characterization of degradation products by liquid chromatography-tandem mass spectrometry (LC-MS/MS) studies in solution form was done, and the possible mechanism for the formation of degradants is discussed. Fenofibrate was subjected to different hydrolytic stress conditions and thermal stress condition (in solid form). Successful separation of drug from degradants was achieved on a C18 column using water-acetonitrile (25:75 v/v) as the mobile phase. Other high-performance liquid chromatography (HPLC) parameters were: flow rate, 1 mL min-1; detection wavelength, 286 nm; column temperature, 25 °C; and injection volume, 20 μL. The method was validated for linearity, precision, accuracy, robustness, and specificity and was stability-indicating one, based on the specificity studies. The drug degraded under acidic, basic, and oxidative hydrolytic stress while it was relatively stable towards neutral hydrolysis and thermal stress. The stressed samples were subjected to LC-MS/MS analysis. On the basis of spectral data, the structures of four degradation products and one interaction product were suggested. Degradation products were characterized to be isopropyl acetate, 2-[4-(4- chlorobenzoyl)phenoxy]-2-methyl propanoic acid, 4-hydroxy benzoic acid, and benzoic acid. The structure of one interaction product was proposed as methyl 2-[4-(4- chlorobenzoyl)phenoxy]-2-methylpropanoate.