Evaluation of automated single mass spectrometry to tandem mass spectrometry function switching for comprehensive drug profiling analysis using a quadrupole time-of-flight mass spectrometer

A liquid chromatographic mass spectrometric strategy for systematic toxicol ogical analysis (STA) is presented using the automatic 'on-the-fly' single mass spectrometry mode to tandem mass spectrometry mode (MS to MS/MS) switc hing abilities of a quadrupole time-of-flight (Q-TOF) instrument. During th e chromatographic run, the quadrupole is initially set to transmit all mass es until (an) ion(s) reaches a certain set threshold. Thereupon, the quadru pole automatically switches to the MS/MS mode, selecting the ion(s), which are subsequently fragmented in the high-efficiency hexapole collision cell, thus generating product ions that are further mass analyzed by the TOF. By limiting the TOF spectral accumulation time in the MS/MS mode to a statist ically acceptable minimum, the quadrupole almost instantly switches back to the MS mode. Qualitative information, comprising the complementary MS ([M + H](+) ion mass) and MS/MS (informative product ion profile) data, as well as quantitative information obtained by integration of the MS extracted io n chromatogram(s), can be obtained in one single acquisition. Optimization of the automatic switching parameters, such as threshold, TOF spectral accu mulation time, detection window and collision energy, was carried out by in jection of a mix of 17 common drugs which were not necessarily baseline sep arated in the chromatographic system used. Indeed, the complete separation of the drugs is not deemed necessary since up to 8 different ions can 'simu ltaneously' be selected for MS/MS if they reach the preset criteria. In add ition, the quantitative performance of the method was defined. In a second phase, the developed method was field-tested. To that end, the resulting da ta from extracts of urine samples were compared with and found to be in clo se concordance with those obtained by a standard toxicological analysis. Th is innovative approach clearly holds the potential for a substantial advanc e in the introduction of LC/MS in STA, Copyright (C) 2000 John Wiley & Sons , Ltd.