UPLC-MS/MS同时测定人血浆中替米沙坦与氨氯地平浓度

An UPLC-MS/MS method for simultaneous determination of telmisartan and amlodipine in human plasma

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,1.7μm)色谱柱,流动相A:甲酸:氨水:水(1:0.2:1000,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.

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.