Yan Tingting, Li Hao, Deng Lili, Guo Yingjie, Yu Weisong, Fawcett J Paul, Zhang Dan, Cui Yimin, Gu Jingkai
Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun 130021, PR China.
J Pharm Biomed Anal. 2008 Dec 1;48(4):1225-9. doi: 10.1016/j.jpba.2008.08.021. Epub 2008 Aug 28.
A rapid and sensitive method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the simultaneous determination of telmisartan and hydrochlorothiazide in human plasma. Sample preparation involved liquid-liquid extraction with diethyl ether-dichloromethane (60:40, v/v). The analytes and internal standard, probenecid, were separated on a Venusil XBP-C(8) column using gradient elution with acetonitrile-10 mM ammonium acetate-formic acid at a flow rate of 1.2 mL/min. Detection was by electrospray negative ionization mass spectrometry using multiple reaction monitoring of the transitions at m/z 513.0-->469.4 for telmisartan, m/z 295.9-->268.9 for hydrochlorothiazide and m/z 283.9-->239.9 for probenecid. For both analytes, the method was linear in the range 1.00-600 ng/mL with intra- and inter-day precision (as relative standard deviation) <or=10.6% and accuracy (as relative error) <or=4.2%. The assay was successfully applied to a pharmacokinetic study in 9 healthy volunteers given a single oral dose of a combination tablet containing telmisartan 80 mg and hydrochlorothiazide 12.5 mg.
已开发出一种使用液相色谱-串联质谱法（LC-MS/MS）同时测定人血浆中替米沙坦和氢氯噻嗪的快速灵敏方法。样品制备包括用乙醚-二氯甲烷（60:40，v/v）进行液-液萃取。分析物和内标丙磺舒在Venusil XBP-C(8)柱上分离，使用乙腈-10 mM醋酸铵-甲酸进行梯度洗脱，流速为1.2 mL/min。通过电喷雾负离子质谱法进行检测，对替米沙坦采用m/z 513.0→469.4的多反应监测，对氢氯噻嗪采用m/z 295.9→268.9，对丙磺舒采用m/z 283.9→239.9。对于两种分析物，该方法在1.00 - 600 ng/mL范围内呈线性，日内和日间精密度（以相对标准偏差计）≤10.6%，准确度（以相对误差计）≤4.2%。该测定法已成功应用于9名健康志愿者的药代动力学研究，这些志愿者单次口服一片含80 mg替米沙坦和12.5 mg氢氯噻嗪的复方片剂。
