Multi-drug and Metabolite Quantification in Postmortem Blood by Liquid Chromatography-High-Resolution Mass Spectrometry: Comparison with Nominal Mass Technology

High-resolution mass spectrometry (HRMS) is being applied in postmortem drug screening as an alternative to nominal mass spectrometry, and additional evaluation in quantitative casework is needed. We report quantitative analysis of benzoylecgonine, citalopram, cocaethylene, cocaine, codeine, dextromethorphan, dihydrocodeine, diphenhydramine, 2-ethylidene-1,5-dimethyl-3,3-diphenyl pyrrolidine, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone and oxymorphone in postmortem blood by ultra-performance liquid chromatography (UPLC)-MSE /time-of-flight (TOF). The method employs analyte-matched deuterated internal standardization and MSE acquisition of precursor and product ions at low (6 eV) and ramped (10-40 eV) collision energies, respectively. Quantification was performed using precursor ion data obtained with a mass extraction window of +/- 5 ppm. Fragment and residual precursor ion acquisitions at ramped collision energies were evaluated as additional analyte identifiers. Extraction recovery of > 60% and matrix effect of < 20% were determined for all analytes and internal standards. Defined limits of detection (10 ng/mL) and quantification (25 ng/mL) were validated along with a linearity analytical range of 25-3,000 ng/mL (R-2 > 0.99) for all analytes. Parallel UPLC-MS E / TOF and UPLC-MS/MS analysis showed comparable precision and bias along with concordance of 253 positive (y = 1.002x + 1.523; R-2 = 0.993) and 2,269 negative analyte findings in 159 postmortem cases. Analytical performance and correlation studies demonstrate accurate quantification by UPLC-MSE/TOF and extended application of HRMS in postmortem casework.