He Xin, Zhang Tingting, Zhao Hongyi, Ma Chen
Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
Metabolites. 2025 Mar 31;15(4):238. doi: 10.3390/metabo15040238.
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. 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 170 and 142 was employed to identify the potential metabolites in precursor screening in vivo, then LC-HRMS and NMR were applied to the metabolites characterization. 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. 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.
SY0916是一种用于治疗慢性免疫炎症性疾病的新型血小板活化因子（PAF）受体拮抗剂，目前正处于II期临床试验阶段。然而，SY0916在体内会迅速转化，这表明需要进行代谢物筛选。根据SY0916及其五种已报道代谢物（M01、M02、M03、M05和M06）相似的质谱裂解模式，采用基于170和142两个特征离子的策略，在体内前体筛选中鉴定潜在代谢物，然后应用液相色谱-高分辨质谱（LC-HRMS）和核磁共振（NMR）对代谢物进行表征。使用LC-HRMS和NMR鉴定出两种I期代谢物（M07和M08）。使用LC-HRMS鉴定出八种II期代谢物，包括六种谷胱甘肽共轭物（M09-M14）和两种磺酸盐共轭物（M15和M16）。总结了SY0916可能的代谢途径及其代谢物质谱的裂解规律。我们使用液相色谱-质谱联用（LC-MS）初步确定了SY0916在大鼠体内的代谢概况，为SY0916的体内代谢研究以及临床研究和未来应用提供了依据。
