A comparison between HPLC-dynamic reaction cell-ICP-MS and HPLC-sector field-ICP-MS for the detection of glutathione-trapped reactive drug metabolites using clozapine as a model compound

摘要: In this study, a novel method was developed for tracing down reactive drug metabolites, the formation of which in human body constitutes an important health risk as result their capability to bind proteins and DNA. Clozapine used model because forms both stable metabolites. Glutathione, complexes with added order trap species clozapine, formed by degradation electrochemical cell, thereby mimicking real metabolism process. The is based on use reversed-phase HPLC chromatographic separation technique inductively coupled plasma-mass spectrometry (ICP-MS) monitoring Cl S. Via Cl-monitoring, all metabolites Cl-containing clozapine can be detected, whereas S-monitoring allows detection S-containing molecule glutathione its conjugates spectral overlap signals 32S+ 34S+ those 16O16O+ 16O18O+, respectively, tackled 2 ways. On one hand, quadrupole-based ICP-MS instrument, equipped dynamic reaction used. O2 gas convert S+ ions sufficient extent into corresponding SO+ species. This did not yield optimal results, due pronounced ArC+ at mass 48 50 upon introduction methanol ICP. other sector-field instrument operated medium resolution permitted interference-free S+-signals. A new type skimmer cone – termed X-skimmer evaluated resulted 4-fold increase sensitivity methanolic environment, providing limit 1 μg L−1 chromatograms obtained via HPLC-SF-ICP-MS differentiation between As result, looks very promising shows potential quantification early stages development when radiolabeled compound yet available.