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Both new and well-known substances keep appearing and disappearing on the market, making it hard to adapt analytical methods in a timely manner. In this study we developed a qualitative screening approach for serum samples by means of liquid chromatography--quadrupole time-of-flight mass spectrometry. Samples were measured in data-dependent auto tandem mass spectrometry mode and identified by fragment spectra comparison, retention time and accurate mass. Approximately 500 NPS, including 195 synthetic cannabinoids, 180 stimulants, 86 hallucinogens, 26 benzodiazepines and 7 others were investigated. Serum samples were fortified to 1\u2009ng\/mL and 10\u2009ng\/mL concentrations to estimate approximate limits of identification (LOIs). Samples were extracted using solid-phase extraction with non-endcapped C18 material and elution in two consecutive steps. Benzodiazepines were eluted in the first step, while substances of other NPS subclasses were distributed among both extracts. To determine LOIs, both extracts were combined. Ninety-six percent (470\/492) of investigated NPS were detected in 10\u2009ng\/mL samples and 88% (432\/492) were detected in 1\u2009ng\/mL samples. Stimulants stood out with higher LOIs, possibly due to instability of certain methcathinone derivatives. However, considering relevant blood concentrations, the method provided sufficient sensitivity for stimulants as well as other NPS subclasses. Data-dependent acquisition was proven to provide high sensitivity and reliability when combined with an information-dependent preferred list, without losing its untargeted operation principle. Summarizing, the developed method fulfilled its purpose as a sensitive untargeted screening for serum samples and allows uncomplicated expansion of the spectral library to include thousands of targets.<\/jats:p>","DOI":"10.1093\/jat\/bkab072","type":"journal-article","created":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T15:09:24Z","timestamp":1623510564000},"page":"592-599","source":"Crossref","is-referenced-by-count":20,"title":["Sensitive Screening of New Psychoactive Substances in Serum Using Liquid Chromatography\u2013Quadrupole Time-of-Flight Mass Spectrometry"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6978-9746","authenticated-orcid":false,"given":"Jan-Niklas","family":"Kleis","sequence":"first","affiliation":[{"name":"Institute of Forensic Medicine, Forensic Toxicology, Johannes Gutenberg University Mainz , Am Pulverturm 3, 55118 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius","family":"Hess","sequence":"additional","affiliation":[{"name":"Institute of Forensic Medicine, Forensic Toxicology, Johannes Gutenberg University Mainz , Am Pulverturm 3, 55118 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Germerott","sequence":"additional","affiliation":[{"name":"Institute of Forensic Medicine, Forensic Toxicology, Johannes Gutenberg University Mainz , Am Pulverturm 3, 55118 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Roehrich","sequence":"additional","affiliation":[{"name":"Institute of Forensic Medicine, Forensic Toxicology, Johannes Gutenberg University Mainz , Am Pulverturm 3, 55118 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"2022071417282504000_R1","article-title":"European Drug Report - Trends and Developments","author":"EMCDDA","year":"2020"},{"key":"2022071417282504000_R2","article-title":"EU Drug Markets Report 2019","author":"EMCDDA and EUROPOL","year":"2019"},{"key":"2022071417282504000_R3","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1515\/cclm-2016-0831","article-title":"Immunoassay screening in urine for synthetic cannabinoids - an evaluation of the diagnostic efficiency","volume":"55","author":"Franz","year":"2017","journal-title":"Clinical Chemistry and Laboratory Medicine"},{"key":"2022071417282504000_R4","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1002\/dta.1702","article-title":"Performance characteristics of an ELISA screening assay for urinary synthetic 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