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A validated screening and confirmation method for 946 drugs and metabolites using LC-QTOF-MS with SWATH acquisition.

作者信息

Sarkisian Maria, Rodda Luke N

机构信息

Office of the Chief Medical Examiner, San Francisco, California 94124, United States.

School of Forensic Sciences, Oklahoma State University, Center for Health Sciences, Tulsa, Oklahoma 74107, United States.

出版信息

J Anal Toxicol. 2025 Jul 1;49(6):407-416. doi: 10.1093/jat/bkaf037.

DOI:10.1093/jat/bkaf037
PMID:40324907
Abstract

A streamlined liquid chromatography quadrupole time-of-flight mass spectrometry method utilizing protein precipitation and filtration extraction was developed to achieve rapid and reliable screening and confirmation for blood and urine matrices. This method targets 946 drugs and metabolites across 35 drug classes via sequential window acquisition of all theoretical mass spectra with variable customized windows to enhance spectral clarity, and was validated per established guidelines to ensure high accuracy and reproducibility. Combined with complementary in-house methods, this approach meets and exceeds the testing requirements outlined in ANSI/ASB standards and recommendations for postmortem, drug-facilitated crime, and Tier I and II driving under the influence of drug analyses. The method demonstrated efficient and sensitive performance, achieving limits of detection as low as 0.1 ng/mL. It accurately identified expected detections across 67 proficiency test samples and 224 authentic case samples, with high accuracy and reliability in the detection of both traditional drugs and novel psychoactive substances. The method employs an in-house built library and incorporates in-batch standards analyzed alongside case samples to ensure contemporaneous identification criteria, making it suitable for confirmation and reporting purposes. By expanding the analytical capabilities to include a vast range of analytes, this method improves the likelihood of identifying substances that may otherwise go undetected and reduces the need for multiple separate tests, thereby enhancing the overall effectiveness of toxicological investigations.

摘要

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