Isolation and Structural Characterization of Finasteride Degradation Products by Preparative HPLC, HRMS, and NMR

Finasteride is a synthetic steroidal drug commonly prescribed for the management of benign prostatic hyperplasia and androgenetic alopecia. The present investigation was undertaken to evaluate the degradation profile of finasteride under stress conditions and to identify the resulting degradation impurities. Stress studies were performed under acidic, alkaline, and oxidative environments following ICH recommendations. LC–MS analysis demonstrated the formation of three degradation products under acidic conditions, whereas negligible degradation was observed under alkaline and oxidative conditions. The degradation products were isolated by preparative HPLC and examined using high-resolution mass spectrometry (HRMS) and multidimensional NMR spectroscopy. Comprehensive spectroscopic evaluation of DP-1 revealed that the degradation process involved cleavage of the tert-butyl amide functionality accompanied by addition of water across the alkene moiety within the steroid nucleus. The structure of DP-1 was successfully established through interpretation of HRMS, ¹H NMR and ¹³C NMR, HSQC, HMBC, and COSY data. A survey of the available literature indicated that DP-1 and the remaining degradation products have not been previously described. The results provide new information regarding the degradation chemistry of finasteride and offer valuable support for impurity profiling, stability studies, and quality control of finasteride pharmaceutical formulations.