Yao Meicun, Gao Jingwen, Li George Q, Xie Zhiyong
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Bioanalysis. 2012 Nov;4(22):2693-703. doi: 10.4155/bio.12.236.
Cytochrome P450 (CYP) enzymes primarily account for the oxidation of xenobiotics. A single run UPLC-MS/MS method was developed to simultaneously detect four metabolites from a probe cocktail to investigate four CYP isozymes. Paracetamol was detected to investigate CYP1A2, 4-hydroxytolbutamide for CYP2C6, 6-hydroxychlorzoxazone for CYP2E1 and dehydronifedipine for CYP3A1. 6-hydroxychlorzoxazone was detected in ESI-negative mode, while the other three were detected in ESI-positive mode.
The method was rapid (2.5 min) and validated to be specific, accurate and precise. It was successfully applied to evaluate the effects of cooked rhubarb on the activities of the four isozymes in rat microsomes. Cooked rhubarb inhibited the activity of CYP2C6 but induced both CYP2E1 and CYP3A1.
This convenient UPLC-MS/MS method was applicable. It could improve the efficiency of future studies estimating the influence of herbs, herbal products or drug entities on the activities of CYP1A2, CYP2C6, CYP2E1 and CYP3A1.
细胞色素P450（CYP）酶主要负责外源性物质的氧化。开发了一种单次运行的超高效液相色谱-串联质谱（UPLC-MS/MS）方法，用于同时检测来自探针混合物的四种代谢物，以研究四种CYP同工酶。检测对乙酰氨基酚以研究CYP1A2，检测4-羟基甲苯磺丁脲以研究CYP2C6，检测6-羟基氯唑沙宗以研究CYP2E1，检测脱氢硝苯地平以研究CYP3A1。6-羟基氯唑沙宗在电喷雾负离子模式下检测，而其他三种在电喷雾正离子模式下检测。
该方法快速（2.5分钟），并经验证具有特异性、准确性和精密度。它成功应用于评估熟大黄对大鼠微粒体中四种同工酶活性的影响。熟大黄抑制CYP2C6的活性，但诱导CYP2E1和CYP3A1的活性。
这种便捷的UPLC-MS/MS方法适用。它可以提高未来评估草药、草药产品或药物实体对CYP1A2、CYP2C6、CYP2E1和CYP3A1活性影响的研究效率。
