OBJECTIVE  To establish a UPLC-HRMS method for simultaneous determination of 43 chemical drugs in blood and apply the method to determine the content of 43 chemical drugs in blood of 100 abnormal death from Hangzhou.

METHODS  Proteins were precipitated using acetonitrile. After centrifugation, the supernatant was collected and dried under a nitrogen stream. The residue was reconstituted with the initial mobile phase, centrifuged, and the supernatant was filtered through a 0.22 μm microporous membrane for instrument analysis. Separation was performed using a C₁₈(150 mm×2.1 mm, 3.0 μm) chromatographic column. The mobile phase consisted of 0.1% formic acid+5 mmol ammonium formate(phase A) and methanol+0.1% formic acid(phase B) with gradient elution. Mass spectrometric detection was carried out using an electrospray ionization source(HESI-II) with simultaneous positive and negative ion scanning and real-time tandem mass spectrometry scanning(Full MS/ddMS2).

RESULTS The linearity of 43 chemical drugs within the range of 10 to 1000 ng·mL⁻¹ was good, with r² ranging from 0.9910 to 0.9998; the limit of quantification was 10 ng·mL⁻¹; the matrix effect was between 79.4% and 99.7%; the method recovery rate was between 80.4% and 97.0%; the intra-day precision(RSD) ranged from 0.1% to 3.2%; and the inter-day precision(RSD) ranged from 0.6% to 9.8%. Using this method, 100 whole blood samples from the Hangzhou Public Security Judicial Identification Center were tested, with 2 samples detected, both of which contained sibutramine.

CONCLUSION  The method is sensitive and accurate for fast detection of 43 chemical drugs in human blood.