One of the neutral reagents used previously to differentiate two isomeric drug metabolites is 2-methoxypropene (MOP). In these experiments, protonation of the analyte was achieved through atmospheric pressure chemical ionization (APCI) in a linear quadrupole ion trap (LQIT) mass spectrometer. The protonated analytes were transferred into the ion trap, isolated and allowed to react with MOP that was continuously introduced into the ion trap (Figure ). Formation of a diagnostic addition product, proton transfer to MOP or no reaction with MOP was monitored. The diagnostic addition product ions were only observed for the protonated sulfoxide drug metabolite and not for its keto-isomer (Figure ). This was verified via studies of several protonated model compounds. Figure . Schematic diagram of a linear quadrupole ion trap mass spectrometer equipped with an APCI ion source and an external reagent mixing manifold. This instrument can be used to detect diagnostic ions formed between a neutral reagent (introduced using the reagent mixing manifold) and a protonated analyte in MS/MS experiments occurring in the ion trap.