Multiclass screening and quantification of drugs and toxicants in whole blood using high-resolution multiple reaction monitoring and information-dependent acquisition under negative electrospray ionization.

Abstract

Drugs and toxicants exhibiting favorable ionization behavior under negative electrospray ionization (ESI-) represent an important group of analytes in toxicological analysis; however, the development of methods optimized for their analysis in this mode remains limited. This study aimed to establish an ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry strategy for the analysis of drugs and toxicants amenable to ESI- in human blood by integrating high-resolution multiple reaction monitoring (MRMHR) with information-dependent acquisition (IDA). The developed method showed good linearity over concentration ranges of 2-800 ng/mL or 5-1000 ng/mL (r² > 0.994), with limits of detection and quantification of 0.5-2 ng/mL and 2-5 ng/mL, respectively. Precision and accuracy met the acceptance criteria, with acceptable matrix effects and recoveries for most analytes. Among 164 authentic blood samples analyzed, 42 had at least one analyte detected, involving 20 compounds in total. All compounds quantified by MRMHR were detected by IDA, and 9 additional compounds outside the quantitative panel were identified. Of these 42 samples, 28 contained at least one compound beyond the predefined MRMHR targets. This strategy enables reliable quantification and expanded screening of drugs and toxicants detectable in ESI-, providing a complementary analytical strategy for toxicological investigations.

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