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We developed a simple nontargeted method using a disposable paper spray cartridge with an integrated solid phase extraction column. This method was used to screen for ~160 fentanyl analogs, synthetic cannabinoids, other synthetic drugs, and traditional drugs of abuse in over 300 authentic overdose samples collected at emergency departments in Indianapolis. A solid phase extraction step was implemented on the paper spray cartridge to enable subnanograms per milliliter synthetic drugs screening in plasma. Analysis was performed on a quadrupole orbitrap mass spectrometer using the sequential window acquisition of all theoretical fragment ion spectra approach in which tandem mass spectrometry was performed using 7\u2009m\/z isolation windows in the quadrupole. Calibration curves with isotopically labeled internal standards were constructed for 35 of the most frequently encountered synthetic and traditional illicit drugs by US toxicology labs. Additional qualitative\u2010only drugs in a suspect screening list were also included. Limits of detection in plasma for synthetic cannabinoids ranged from 0.1 to 0.5 and 0.1 to 0.3\u00a0ng\/mL for fentanyl and its analogs and between 1 and 5\u00a0ng\/mL for most other drugs. Relative matrix effects were evaluated by determining the variation of the calibration slope in 10 different lots of biofluid and found to be between 3% and 20%. The method was validated on authentic overdose samples collected from two emergency departments in Indianapolis, Indiana, from suspected or known overdoses. Commonly detected synthetic drugs included fentanyl related substances, designer benzodiazepines such as flubromazolam, and the synthetic cannabinoid 5F\u2010PB\u201022.<\/jats:p>","DOI":"10.1002\/dta.3687","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:30:19Z","timestamp":1712536219000},"page":"138-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Plasma drug screening using paper spray mass spectrometry with integrated solid phase extraction"],"prefix":"10.1002","volume":"17","author":[{"given":"Hannah","family":"Zimmerman\u2010Federle","sequence":"first","affiliation":[{"name":"Department of Chemistry and Chemical Biology Indiana University\u2013Purdue University Indianapolis  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Indiana University\u2013Purdue University Indianapolis  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Dowling","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Indiana University\u2013Purdue University Indianapolis  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Indiana University\u2013Purdue University Indianapolis  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rusyniak","sequence":"additional","affiliation":[{"name":"School of Medicine Indiana University  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Avera","sequence":"additional","affiliation":[{"name":"School of Medicine Indiana University  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-0497","authenticated-orcid":false,"given":"Nicholas E.","family":"Manicke","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Indiana University\u2013Purdue University Indianapolis  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,7]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"2018 National Drug Threat Assessment United States Drug Enforcement Administration","year":"2018"},{"key":"e_1_2_6_3_1","unstructured":"World Drug Report.2019;United Nations publication 2019. doi:10.18356\/a4dd519a\u2010en."},{"key":"e_1_2_6_4_1","volume-title":"EMCDDA\u2013Europol 2017 Annual Report on the Implementation of Council Decision 2005\/387\/JHA","author":"Addiction, E. 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