UPLC-MS/MS法同时测定人血浆中氯沙坦及其代谢物浓度  

An UPLC-MS/MS method for simultaneous determination of losartan and metabolites in human plasma

作　　者：夏伯姗 王振磊 李岱庆 王曼[1,2] 王鸿芡 张梅 秦永平[2] 南峰[2] 向瑾[2] XIA Boshan;WANG Zhenlei;LI Daiqing;WANG Man;WANG Hongqian;ZHANG Mei;QIN Yongping;NAN Feng;XIANG Jin(The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine,Key Laboratory of Systematic Research,Development and Utilization of Chinese Medicine Resources in Sichuan Province,Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST,School of Pharmacy,C;GCP Center/Institute of Drug Clinical Trials,West China Hospital,Sichuan University,Chengdu 610041,China;Yangtze River Pharmaceutical Group-Sichuan Hairong Pharmaceutical Co.,Ltd.,Chengdu 610041,China)

机构地区：[1]成都中医药大学药学院中药材标准化教育部重点实验室中药资源系统研究与开发利用省部共建国家重点实验室培育基地,四川成都611137 [2]四川大学华西医院国家药物临床试验机构临床药理研究室,四川成都610041 [3]扬子江药业集团四川海蓉药业有限公司,四川成都610041

出　　处：《中国测试》2018年第7期61-67,82,共8页China Measurement & Test

摘　　要：建立UPLC-MS/MS法测定人血浆中氯沙坦及代谢物氯沙坦羧酸的浓度,以用于氯沙坦的药代动力学研究。采用Sepax GP-C18(2.1 mm×50 mm,1.8μm)色谱柱,以0.15%甲酸-0.04%氨水-水(超声20 min后,加入0.01%氨水)为水相,0.15%甲酸-0.04%氨水-98%乙腈为有机相。梯度洗脱,流量为0.3 mL/min。以d4-氯沙坦、d4-氯沙坦羧酸作内标,血浆样本用乙腈一步沉淀蛋白,采用多反应离子监测,正离子模式扫描,电喷雾离子源。结果表明:氯沙坦在2.0~2 000 ng/mL范围内,氯沙坦羧酸在2.4~2 400 ng/mL范围内线性良好;氯沙坦及内标的保留时间为1.16 min左右,氯沙坦羧酸及内标的保留时间为1.26 min左右;氯沙坦、氯沙坦羧酸提取回收率分别为109.9%、97.55%;精密度、基质效应经内标校准后均合格;稳定性各项数据均符合相关要求。该法快速、灵敏、专属性强、重现性好,适用于氯沙坦及其代谢物的血药浓度测定。To develop an accurate and sensitive UPLC-MS/MS method for simultaneous determination of losartan and its active metabolites losartan carboxylic acid in human plasma to study pharmacokinetic of losartan in human.Using SepaxGP-C18(2.1 mm×50 mm,1.8μm)column with 0.15%formic acid-0.04%ammonia-water(ultrasonic for 20 min,add 0.01%ammonia water)as the aqueous phase,0.15%formic acid-0.04%ammonia-98%acetonitrile as the organic phase,the flow rate was 0.3 mL/min,gradient elution.D4-losartan and d4-losartan carboxylic acid were used as the internal standard.Human plasma samples were deproteinized with acetonitrile.An electron spray ionization(ESI)was applied and operated in the positive multiple reaction monitoring(MRM)mode.In the plasma samples,the calibration curve for losartan and losartan carboxylic acid was in the range of 2.0-2 000 ng/mL and 2.4-2 400 ng/mL,respectively.The retention time of losartan and its internal standard were 1.16 min while the retention time of losartan carboxylic acid and its internal standard were 1.26 min.Pretreatment recovery was 109.9%,97.55%.Accuracy,precision and matrixes effect after internal standard calibration are comply with relevant requirements.The method is simple,rapid,sensitive and accurate for the determination of losartan and metabolites in human plasma and to be suitable for the pharmacokinetic study.

关 键 词：药动学 UPLC-MS/MS 氯沙坦 氯沙坦羧酸 

分 类 号：R285[医药卫生—中药学]