Hemmer Selina, Ninnig Maximilian, Wagmann Lea, Manier Sascha K, Meyer Markus R
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Homburg, Germany.
Drug Test Anal. 2025 Sep;17(9):1502-1515. doi: 10.1002/dta.3855. Epub 2025 Jan 19.
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.
快速、全面的定性和定量分析程序在全天候紧急毒理学(ET)中至关重要,以支持急性中毒的诊断和治疗,并监测其进展以及解毒策略的效果。本研究旨在使用自动液相色谱(LC)-线性离子阱质谱(MS)筛查系统,对人血浆中的62种药物以及7种活性代谢物进行同时定性和定量分析。通过液液萃取进行样品制备,并使用电子存储的五点校准法测定血浆浓度。根据包括选择性、残留、准确性、精密度和基质效应在内的ET国际指南和建议进行验证。最后,使用病例样本和能力验证测试评估该方法的适用性。该方法对所有分析物均显示出选择性,无明显残留或基质效应。除10种分析物外,所有测试分析物均能满足ET推荐的准确性和精密度要求。对患者血浆样本进行了分析,并与参考LC-串联MS或气相色谱-MS方法获得的结果进行了比较。此外,该方法的适用性得到了证明。它为69种分析物提供了快速、稳健且可靠的血浆筛查,并对ET中相关的59种分析物进行了额外定量。使用电子存储的五点校准法和简化的“一键打印解决方案”,可以直接评估分析物的血浆水平。