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

Abstract

A liquid chromatographic mass spectrometric strategy for systematic toxicological analysis (STA) is presented using the automatic ‘on‐the‐fly’ single mass spectrometry mode to tandem mass spectrometry mode (MS to MS/MS) switching abilities of a quadrupole time‐of‐flight (Q‐TOF) instrument. During the chromatographic run, the quadrupole is initially set to transmit all masses until (an) ion(s) reaches a certain set threshold. Thereupon, the quadrupole 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 statistically 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 ion chromatogram(s), can be obtained in one single acquisition. Optimization of the automatic switching parameters, such as threshold, TOF spectral accumulation time, detection window and collision energy, was carried out by injection of a mix of 17 common drugs which were not necessarily baseline separated in the chromatographic system used. Indeed, the complete separation of the drugs is not deemed necessary since up to 8 different ions can ‘simultaneously’ be selected for MS/MS if they reach the preset criteria. In addition, the quantitative performance of the method was defined. In a second phase, the developed method was field‐tested. To that end, the resulting data from extracts of urine samples were compared with and found to be in close concordance with those obtained by a standard toxicological analysis. This innovative approach clearly holds the potential for a substantial advance in the introduction of LC/MS in STA. Copyright © 2000 John Wiley & Sons, Ltd.

New trends in hair analysis and scientific demands on validation and technical notes

“…Also Marquet et al developed a general unknown screening procedure using a QTrap [93]. Others described screening procedures using ion trap MS [94], a quadrupole time-of-flight (Q-TOF) instrument switching automatically from MS to MS/MS mode when exceeding a given threshold [95] or exact mass measurement of product ions for identification of unknown compounds [96]. Such sophisticated screening procedures have to be adapted to hair testing in the future.…”

Combined drug screening and confirmation by liquid chromatography time-of-flight mass spectrometry with reverse database search

“…The "TOF revolution" [2] initially emerged from the pharmaceutical industry and drug discovery [3,4], and when combined with LC or gas chromatography (GC), the technique was readily adapted to other application areas of small molecule identification. Forensic [5,6] and clinical toxicology applications [7] together with steroid identification [8] were among the pioneer fields, soon followed by pesticide analysis [9,10]. Since then, numerous papers have been published dealing with identification by accurate mass measurement and often combined with a database or spectrum library search, as recently reviewed within forensic toxicology [11,12], doping control [13], and pesticide analysis [14].…”

Optimization of solid-phase extraction for a liquid chromatographic–tandem mass spectrometric general unknown screening procedure by means of computational techniques

“…The substances of interest, unknown beforehand in number or composition, are all to be isolated at a yield as high as possible while those interfering substances from the biological matrix are removed. After all, IDA is a technique based on the automatic "on-the-fly" MS to MS-MS switching abilities of, in our case, a quadrupole time-of-flight (Q-TOF) system [6]. Precursor ions, observed in a MS survey scan, are automatically selected for interrogation by MS-MS, once a predefined intensity threshold is exceeded.…”

“…Precursor ions, observed in a MS survey scan, are automatically selected for interrogation by MS-MS, once a predefined intensity threshold is exceeded. A major criterion which governs the applicability of IDA in systematic toxicological analysis (STA) is the lack of interferents which initiate and thus temporarily "occupy" the MS-MS channels, effectively blinding the method to the compounds of real toxicological interest [6]. Consequently, the applicability of such an IDA method largely depends on the quality of the extraction procedure for a biological sample.…”