Mass spectral fragmentation reactions of a therapeutic 4-azasteroid and related compounds

Mass spectra were acquired for a therapeutic 4-azasteroid (dutasteride), an d some related compounds, using various ionization conditions (EI, CI, APCI and ESI) in both positive and negative ion modes. The ionization and fragm entation behavior of the compound dutasteride, its precursors and several a nalogs is reported. Positive atmospheric pressure chemical ionization (APCI +) and positive electrospray ionization (ESI+) produced distinctive collisi on-induced dissociation (CID) spectra for the respective [MH](+) ions of du tasteride. The spectral differences are attributed to ion populations havin g either different structures or different internal energy distributions (a s a consequence of the method of ionization). Irrespective of their origin, the protonated molecules undergo interesting fragmentation reactions when collisionally activated. The identity of the major fragmentation products w as confirmed by accurate mass measurement. The negative APCI mass spectrum of dutasteride displays extensive dehydrohalogenation, apparently due to th e thermal component of the APCI process. Some of the resulting radical anio ns display remarkable stability toward collisional decomposition. Details o f the fragmentation behavior for the negative ion species and their relatio nship to the positive ion results are discussed. (C) 2001 American Society for Mass Spectrometry.