Identification of an N-(hydroxysulfonyl)oxy metabolite using in vitro microorganism screening, high-resolution and tandem electrospray ionization mass spectrometry

Preliminary metabolic profiling of a drug under pre-clinical development re vealed the presence of a minor unknown metabolite with a positive ion elect rospray ionization (ESI) mass spectrum identical to that of the unchanged c ompound. Since the low concentration of the compound did not allow any addi tional experiments, preparative bioconversion using fungi was used to obtai n a substantial amount of the molecule. Negative ion ESI-MS and tandem mass spectrometry (MS/MS) in combination with accurate mass measurements obtain ed on a quadrupole/time-of-flight instrument (Q-TOF) led to the positive id entification of a hydroxylamide sulfoconjugated metabolite. Copyright (C) 2 000 John Wiley & Sons, Ltd.