ESI-MS/MS library of 1,253 compounds for application in forensic and clinical toxicology

Abstract

An electrospray ionization tandem mass spectrometry (ESI-MS/MS) library which contains over 5,600 spectra of 1,253 compounds relevant in clinical and forensic toxicology has been developed using a hybrid tandem mass spectrometer with a linear ion trap. Pure compound solutions-in some cases solutions made of tablets-were prepared and 1 to 2,000 ng of each compound were injected into the system using standard reversed-phase analytical columns with gradient elution. To obtain maximum mass spectral information enhanced product ion spectra were acquired with positive and/or negative ionization at low, medium, and high collision energies and additionally applying collision energy spread. In this mode, all product ions generated by the different collision energies are trapped in the linear ion trap prior to their detection. The applicability of the library for other types of hybrid tandem mass spectrometers with a linear ion trap of the same manufacturer as well as a standard triple-quadrupole tandem mass spectrometer has been investigated with a selection of compounds. The spectra of the developed library can be used to create methods for target analysis, either screening methods or quantitative procedures by generating transitions for multiple reaction monitoring. For those procedures, suitable transitions and convenient collision energies are selected from the library. It also has been utilized to identify compounds with a multi target screening approach for clinical and forensic toxicology with a standardized and automated system. The novel aspects compared to our former library produced with a standard triple-quadrupole mass spectrometer are the enlargement of the ESI-MS/MS library and the additional acquisition of spectra with collision energy spread.

Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis

“…The concept of SWATH MS acquisition and targeted data analysis should be easily extendable to other classes of biomolecules such as metabolites, lipids, and more that are also frequently studied by LC-MS/MS and for which fragment ion spectral libraries have been developed (41)(42)(43)(44)(45)(46). Also, the possibility to re-examine patterns in the SWATH MS data sets enables new opportunities for finding modified residues and search for the presence of previously unexpected analytes (Fig.…”

Fragmentation of toxicologically relevant drugs in positive‐ion liquid chromatography–tandem mass spectrometry

“…An alternative procedure, also involving the use of a quadrupole-linear ion trap hybrid instrument, was proposed by the group of Weinmann, where targeted SRM with up to 700 transitions was used as a survey analysis mode, and enhanced product ion spectra were searched against a mass spectral library Dresen et al, 2009Dresen et al, , 2010. Whereas the latter procedure seems to be a versatile and sensitive approach to STA, one may argue that the inherent targeted nature of the use of SRM in the survey mode excludes to answer the more general clinical question whether an individual had been intoxicated at all rather than intoxicated with a compound from a predefined list (Sauvage & Marquet, 2010).…”

Laboratory diagnostics in acute poisoning: critical overview

“…Depending on the concentration of a compound not envisaged for detection and identification, and the exact method applied in the mass spectrometer, it might be that this additional substance cannot be detected at all in the chromatogram. This makes the LC-MS/MS screening methods to targeted screening methods with a distinct number of compounds which can be identified (24). Dresen et al have recently published an ESI-MS/MS library containing 1253 compounds, which could be applied not only on the type of instrument on which the spectra have been recorded, but also on two other instrument types from the same manufacturer using a linear ion trap for detection.…”