Comprehensive Qualitative Drug Screening in Emergency Toxicology Using an Automated LC-MSn System:Simultaneous Quantification of Relevant Drugs and Metabolites in Blood Plasma

Abstract

Rapid and comprehensive qualitative and quantitative analytical procedures are crucial in 24/7 emergency toxicology (ET) to support diagnosis and treatment of acute intoxications and to monitor their progression and efficacy of detoxification strategies. This study aimed to develop the simultaneous qualitative and quantitative analysis of 62 drugs, as well as seven active metabolites in human blood plasma using an automated liquid chromatography (LC)-linear ion trap mass spectrometry (MS) screening system. Sample preparation was conducted by liquid–liquid extraction, and plasma concentrations were determined using an electronically stored 5-point calibration. Validation was performed according to international guidelines and recommendations for ET including selectivity, carry-over, accuracy, precision, and matrix effects. Finally, applicability was evaluated using case samples and proficiency tests. The method demonstrated selectivity for all analytes, with no significant carry-over or matrix effects. Accuracy and precision recommended for ET could be fulfilled for all tested analytes, except for 10 analytes. Patient plasma samples were analyzed and compared with results obtained by reference LC-tandem MS or gas chromatography-MS methods. Furthermore, the applicability of the method could be demonstrated. It provides a fast, robust, and reliable blood plasma screening for 69 analytes and an additional quantification of 59 analytes relevant in ET. The use of an electronically stored 5-point calibration and a simplified “push and print solution” allows for straightforward assessment of blood plasma levels of the analytes.