Characterization of Ten Novel Metabolites of a PAF Antagonist SY0916 in Rats Using LC-MS and NMR

<b>Background:</b> SY0916 is a novel PAF receptor antagonist used to treat chronic immune-inflammatory diseases and is currently undergoing phase II clinical trials. However, SY0916 is rapidly transformed in vivo, suggesting a demand for metabolite screening. <b>Methods:</b> According to the similar MS fragmentation patterns of SY0916 and its five reported metabolites (M01, M02, M03, M05, and M06), a strategy based on two characteristic ions of <i>m/z</i> 170 and <i>m/z</i> 142 was employed to identify the potential metabolites in precursor screening in vivo, then LC-HRMS and NMR were applied to the metabolites characterization. <b>Results:</b> Two phase I metabolites (M07 and M08) were identified using LC-HRMS and NMR. Eight phase II metabolites, including six glutathione conjugates (M09-M14) and two sulfonate conjugates (M15 and M16), were identified using LC-HRMS. The possible metabolic pathways of SY0916 and fragmentation regularities of mass spectra of its metabolites were summarized. <b>Conclusions:</b> We preliminarily determined the metabolic profile of SY0916 in rats using LC-MS, providing insight into the metabolism of SY0916 in vivo and a basis for clinical studies and future applications.