Characterization of the degradation products of bambuterol using LCMS-QTOF and NMR

Abstract

Bambuterol was subjected to forced degradation studies as per International Conference on Harmonization (ICH) guidelines. Bambuterol was stable in thermal degradation conditions while it was found to be labile in acidic, basic, neutral, oxidative and photolytic stress conditions. In all, 12 degradation products (DP) were formed. Four degradation products were generated in both the acid and the neutral hydrolysis studies (DP-1, DP-3, DP-4 and DP-11). Five degradation products (DP-3, DP-4, DP-6, DP-8 and DP-11) were formed in the base hydrolysis study. Oxidative conditions gave six degradation products (DP-2, DP-4, DP-5, DP-7, DP-9 and DP-11). The photolytic study also resulted in six degradation products (DP-2, DP-4, DP-5, DP-8, DP-10 and DP-12). The major degradation products (DP-1, DP-3, DP-4, DP-9) were isolated with semi-preparative high pressure liquid chromatography (SP-HPLC) and characterized using 1D (¹H NMR, ¹³C NMR, DEPT) and 2D-NMR studies (COSY). Characterization of the degradation products formed in extremely small quantities was carried out using LCMS-QTOF and MS/MS fragmentation studies.