作者：李艳玲^1,2, 王曼³, 王振磊², 王鸿芡², 夏伯姗^1,2, 岳娇², 梁秀芳², 南峰², 向瑾², 王永生², 秦永平², 张梅¹

作者单位：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. 中国医学科学院北京协和医学院药物研究所 天然药物生物活性物质与功能国家重点实验室, 北京 100050

关键词：UPLC-MS/MS;替米沙坦;氨氯地平;血药浓度

摘要：

建立UPLC-MS/MS法同时测定人血浆中替米沙坦与氨氯地平的浓度，用于研究替米沙坦/氨氯地平片的药代动力学。采用Waters BEH C18 （2.1 mm×50 mm，1.7 μm） 色谱柱，流动相A：甲酸：氨水：水（1：0.2：1 000，v/v/v），流动相B：甲酸：氨水：乙腈：水（1：0.2：950：50，v/v/v/v），进行梯度洗脱，流量0.3 mL/min，以d3-替米沙坦、d4-氨氯地平作内标。血浆样本液液萃取后，采用SHIMADZU SIL-30 AD型UPLC进样分离，美国AB Sciex QTRAP 5500质谱仪在MRM模式下检测。结果表明：替米沙坦在0.50~500 ng/mL范围内，氨氯地平在0.05~8.00 ng/mL范围内线性良好；替米沙坦及内标的保留时间均为1.43 min，氨氯地平及内标的保留时间均为1.31 min；替米沙坦萃取回收率103.0%~104.2%、氨氯地平萃取回收率54.6%~66.5%；方法的特异性、灵敏性、线性、精密度、准确度、基质效应以及稳定性验证数据均符合相关要求。该法快速、灵敏、专属性强、重现性好，适用于替米沙坦/氨氯地平的血药浓度测定。

An UPLC-MS/MS method for simultaneous determination of telmisartan and amlodipine in human plasma
LI Yanling^1,2, WANG Man³, WANG Zhenlei², WANG Hongqian², XIA Boshan^1,2, YUE Jiao², LIANG Xiufang², NAN Feng², XIANG Jin², WANG Yongsheng², QIN Yongping², ZHANG Mei¹
1. 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, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China;
2. GCP Center/Institute of Drug Clinical Trials, West China Hospital, Sichuan University, Chengdu 610041, China;
3. State Key Laboratory of Bioactive Substance and Function of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Perking Union Medical College, Beijing 100050, China
Abstract: A specific and sensitive UPLC-MS/MS method was developed and validated for the simultaneous determination of telmisartan and amlodipine in human plasma to study pharmacokinetic of telmisartan/amlodipine tablets. The plasma samples were separated on a Waters BEH C18 column (2.1mm×50 mm, 1.7 μm) column with the mobile phases A: formic acid-ammonium hydroxide-water (1∶0.2∶1 000, v/v/v) and B: formic acid-ammonium hydroxide-Acetonitrile-H₂O (1∶0.2∶950∶50, v/v/v/v), gradient elution. The flow rate was 0.3 mL/min. The samples was detected under the multiple-reaction monitoring mode by a Qtrap 5500 triple quadrupole-linear ion trap mass spectrometer. The linear range of telmisartan and amlodipine were 0.50-500 ng/mL and 0.05-8.00 ng/mL, respectively. The retention time of telmisartan and internal standard were 1.43 min while the retention time of amlodipine and its internal standard were 1.31 min; the mean recoveries of telmisartan and amlodipine was 103.0%~104.2% and 54.6%~66.5%, respectively. The method was fully verified in terms of sensitivity, specificity, linearity, precision, accuracy, matrix effect and stability, and all the data are comply with the relevant requirements. The method is rapid, sensitive, specific, and reproducible for the determination of telmisartan/amlodipine in human plasma.
Keywords: UPLC-MS/MS;telmisartan;amlodipine;plasma concentration
2019, 45(7):66-73  收稿日期: 2019-01-21;收到修改稿日期: 2019-03-06
基金项目:
作者简介: 李艳玲(1994-),女,山西运城市人,硕士研究生,专业方向为药物分析
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