title: Postmortem drug screening by non-targeted and targeted ultra-performance liquid chromatography-mass spectrometry technology.
abstract: In the medical examiner setting, comprehensive drug screening is an essential analytical tool in the investigation of cause and manner of death.We have validated non-targeted and targeted screening assays for drugs and metabolites using ultra-performance liquid chromatography (UPLC) interfaced with mass spectrometry (MS) in single and tandem stages. For non-targeted screening by UPLC-MS electrospray interface, in-source fragmentation was used along with MS scanning (m/z 80-650) and library search for over 700 drug and metabolite analytes. Targeted detection of over 200 analytes by UPLC-MS-MS was performed with dual transition ion monitoring. Validation studies confirmed reproducibility of both mass spectra produced by in-source fragmentation and transition ion ratios by collision-cell dissociation. Lower limit of detection by UPLC-MS (10-150 ng/mL) and UPLC-MS-MS (1-50 ng/mL) was determined for a subset of drugs and correlated with extraction recovery and matrix effect. Drug findings by UPLC-MS and UPLC- MS-MS were compared with gas chromatography-mass spectrometry (GC-MS) screening in postmortem blood from 410 medical examiner cases with 1121 positive drug findings by all methods. Accuracy, based on results of confirmation testing, was high (98-99%) across all screening assays and detection sensitivity by GC-MS (71%), UPLC-MS (73%), and UPLC-MS-MS (76%) was determined. UPLC-MS plus UPLC-MS-MS screening resulted in the highest drug detection rate (95%) and provided optimal dual-screening for the postmortem casework.
authors.affiliation: Forensic Toxicology Laboratory, Department of Pathology and Laboratory Medicine, Albany Medical Center Hospital and College, Albany, New York, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Rosano
authors.forename: Michelle
authors.initials: M
authors.lastname: Wood
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Swift
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001344:Autopsy; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D053593:Forensic Toxicology / Q000379:methods* / Q000592:standards; D006801:Humans; D007223:Infant; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000097:blood*; D011786:Quality Control; D015203:Reproducibility of Results; D015813:Substance Abuse Detection / Q000379:methods* / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D004364:Pharmaceutical Preparations