Blood plasma level determination using an automated LC-MSn screening system and electronically stored calibrations exemplified for 22 drugs and two active metabolites often requested in emergency toxicology.

Abstract

Fast and comprehensive qualitative and quantitative methods preferably by gas chromatography-mass spectrometry (GC-MS) and/or liquid chromatography-mass spectrometry (LC-MS) are needed to support the (differential) diagnosis of acute poisonings in emergency toxicology. One option is a commercially available qualitative screening solution based on LC-MSn (Bruker Daltonik Toxtyper™, TT). Identified and toxicologically relevant compounds should be quantified to assess severity of poisonings. The aim of the present study was to test the TT system for quantification simultaneous with the screening process in blood plasma exemplified for 22 relevant drugs and two active metabolites. A standard liquid-liquid extraction was used for sample work-up followed by 1:5 dilution of the final extracts. They were analyzed using the TT system consisting of a Bruker amaZon speed ion trap and a Thermo Fisher Dionex Ultimate 3000 LC system. Plasma levels were assessed using full-scan data and an electronically stored five-point calibration. The calibration model was linear for the studied ranges and could be used for at least two months. The method was validated according to international guidelines. The acceptance criteria recommended for emergency toxicology for accuracy and precision were fulfilled for all tested compounds, but bromazepam, lorazepam, oxycodone, and prothipendyl could reliably be determined only above the therapeutic range. In conclusion, the presented procedure allowed the combination of a comprehensive LC-MSn screening with fast automated assessment of plasma levels for emergency toxicology of tested compounds.