title: Drug screening in medical examiner casework by high-resolution mass spectrometry (UPLC-MSE-TOF).
abstract: Postmortem drug findings yield important analytical evidence in medical examiner casework, and chromatography coupled with nominal mass spectrometry (MS) serves as the predominant general unknown screening approach. We report screening by ultra performance liquid chromatography (UPLC) coupled with hybrid quadrupole time-of-flight mass spectrometer (MS(E)-TOF), with comparison to previously validated nominal mass UPLC-MS and UPLC-MS-MS methods. UPLC-MS(E)-TOF screening for over 950 toxicologically relevant drugs and metabolites was performed in a full-spectrum (m/z 50-1,000) mode using an MS(E) acquisition of both molecular and fragment ion data at low (6 eV) and ramped (10-40 eV) collision energies. Mass error averaged 1.27 ppm for a large panel of reference drugs and metabolites. The limit of detection by UPLC-MS(E)-TOF ranges from 0.5 to 100 ng/mL and compares closely with UPLC-MS-MS. The influence of column recovery and matrix effect on the limit of detection was demonstrated with ion suppression by matrix components correlating closely with early and late eluting reference analytes. Drug and metabolite findings by UPLC-MS(E)-TOF were compared with UPLC-MS and UPLC-MS-MS analyses of postmortem blood in 300 medical examiner cases. Positive findings by all methods totaled 1,528, with a detection rate of 57% by UPLC-MS, 72% by UPLC-MS-MS and 80% by combined UPLC-MS and UPLC-MS-MS screening. Compared with nominal mass screening methods, UPLC-MS(E)-TOF screening resulted in a 99% detection rate and, in addition, offered the potential for the detection of nontargeted analytes via high-resolution acquisition of molecular and fragment ion data.
authors.affiliation: 1Department of Pathology and Laboratory Medicine, Forensic Toxicology Laboratory, Albany Medical Center Hospital and College, 43 New Scotland Avenue, Albany, NY 12208, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Rosano
authors.forename: Michelle
authors.initials: M
authors.lastname: Wood
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ihenetu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Swift
mesh_terms: D000328:Adult; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003334:Coroners and Medical Examiners; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood*; D005260:Female; D053593:Forensic Toxicology / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000097:blood*; D011180:Postmortem Changes; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations