HPLC-MS/MS法同时测定人血浆中替米沙坦和氢氯噻嗪的浓度

Determination of Telmisartan and Hydrochlorothiazide in Human Plasma by HPLC-MS/MS

建立高效液相色谱-串联质谱（HPLC—MS／MS）法同时测定人血浆中替米沙坦和氢氯噻嗪的浓度。选用Zorbax Eclipse XDB-C 18色谱柱，以乙腈-5mmol／L乙酸铵为流动相，采用梯度洗脱进行分离，样品用V（乙醚）：V（二氯甲烷）=60：40的溶液，液-液萃取后进样，选用3200Q-Trap型质谱仪的多重反应监测（MRM）扫描方式进行检测。替米沙坦线性范围为1．0～1000．0μg／L，氢氯噻嗪线性范围为0．6～200．0μg／L，定量下限分别为1．0和0．6μg／L。准确度与精密度结果显示，方法日间、日内变异均小于15％，相对偏差分别为替米沙坦-5．6％～4．3％、氢氯噻嗪-6．3％～2．7％。替米沙坦和氢氯噻嗪的低、中、高3个浓度提取回收率均大于50％，稳定性较好。该方法可用于人体替米沙坦和氢氯噻嗪血药浓度的同时监测，以及复方制剂的人体药代动力学研究。

Telmisartan and hydrochlorothiazide in human plasma were determined by high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）. Telmisartan, hydrochlorothiazide and the internal standard were extracted from plasma using V （diethyl ether） ： V （dichloromethane）=60：40, and separated on a Zorbax Eclipse XDB- C 18 column using acetonitrile-5 mmol/L ammonium acetate as mobile phase by gradient elution. Detection was carried out by multiple reaction monitoring （MRM） on a 3200Q-Trap LC-MS/MS system. The assay is linear over the range 1.0-1 000.0 μg/L with a lower limit of quantitation of 5.0 μg/L for telmisartan, and linear over the range 0. 6-200. 0 μg/L with a lower limit of quantitation of 0. 6 μg/L for hydrochlorothiazide. Intra- and inter-day precision are less than 15%. The relative deviations are in the range of -5.6%-4.3% for telmisartan, and --6. 3%--2. 7% for hydrochlorothiazide. The recoveries of telmisartan and hydrochlorothiazide are more than 50%, and stabilities are good.