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However, such multianalyte procedures can be difficult to develop and maintain with sufficient robustness in the laboratory. One aspect of this is the tedious, manual preparation of spiking solutions containing such a great number of analytes. Therefore, the current study aimed to develop and validate a fast, simple, and robust liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) method for the quantification of 82 classic drugs and to evaluate an alternative autosampler\u2010assisted automated approach for the preparation of spiking solutions. Simple protein precipitation of 200\u2010\u03bcL whole blood was used followed by analysis by reversed\u2010phase LC\u2013MS\/MS in advanced scheduled multiple reaction monitoring (MRM) mode. The method was fully validated according to international guidelines, including selectivity, recovery, matrix effects, linearity, bias\/imprecision, processed\u2010sample stability, and limits. Validation criteria were fulfilled for all analytes except for buprenorphine and five benzodiazepines. In the context of a multianalyte procedure, a (multipurpose) autosampler\u2010assisted automatic preparation of calibrator spiking solutions proved comparable to manual preparation. Thus, automated preparation can overcome the frequently performed manual, time\u2010consuming, and error\u2010prone steps of multianalyte approaches and still allow for customized calibration ranges. Since its introduction, more than 8000 cases have been measured with the presented method, and 35 proficiency tests have been passed.<\/jats:p>","DOI":"10.1002\/dta.3794","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T03:49:06Z","timestamp":1726458546000},"page":"954-988","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Multianalyte Approach\u2014Including Automated Preparation of Calibrators\u2014for Validated Quantification of 82 Drugs in Whole Blood by Liquid Chromatography\u2013Tandem Mass Spectrometry"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8983-2353","authenticated-orcid":false,"given":"Andrea\u00a0E.","family":"Steuer","sequence":"first","affiliation":[{"name":"Department of Forensic Pharmacology &amp; Toxicology, Institute of Forensic Medicine University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Forensic Pharmacology &amp; Toxicology, Institute of Forensic Medicine University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3283-606X","authenticated-orcid":false,"given":"Thomas","family":"Kraemer","sequence":"additional","affiliation":[{"name":"Department of Forensic Pharmacology &amp; Toxicology, Institute of Forensic Medicine University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra\u00a0N.","family":"Poetzsch","sequence":"additional","affiliation":[{"name":"Department of Forensic Pharmacology &amp; Toxicology, Institute of Forensic Medicine University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-007-1271-6"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-008-2338-8"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2005.01.014"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.12.008"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.06.028"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00414-005-0042-1"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2021.122867"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-011-4959-6"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2014.12.084"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.1923"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-015-9023-5"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/bkaa032"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2023.115315"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.2175"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.4736"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.4459"},{"key":"e_1_2_6_18_1","unstructured":"J. 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