高效液相色谱法测定中国健康志愿者血清中坎地沙坦及坎地沙坦西酯片的人体药动学

Determination of candesartan in human serum using high performance liquid chromatography and pharmacokinetics of candesartan cilexetil tablets in Chinese healthy volunteers

目的建立高效液相色谱-荧光检测法测定人血清中坎地沙坦的方法,考察坎地沙坦西酯片在中国健康志愿者体内的药动学参数。方法以萘普生为内标,按内标法定量。血清样品经盐酸酸化后,加入甲基叔丁基醚萃取,离心分离,取上清液置于已加入1,3-丙二醇的离心管,吹干后用流动相溶解进样。色谱柱：YMC ODS柱（250mm×4.6mm,5μm）,柱温：30℃;流动相：10mmol/L磷酸二氢钾溶液（磷酸调pH到3.0）∶乙腈=60∶40,流速：1.0mL/min。荧光检测波长：λex270nm,λem390nm。用该方法测定20名健康志愿者口服坎地沙坦西酯片8mg后血清中的药物浓度,进行药动学分析。结果坎地沙坦和萘普生的保留时间分别为10.4min和16.5min;坎地沙坦的线性范围是1.01～202μg/L;日内、日间RSD小于10.39%;方法回收率在94.05%～112.80%范围内。结论此方法适合人体药动学的血样分析,结果准确可靠。

Objective To develop a sensitive and specific method for the determination of candesartan in human serum and to study the pharmacokinetics characteristics of candesartan cilexetil tablets in Chinese healthy volunteers using this method. Methods The samples were extracted from serum with diethyl ether. Chromatography was performed on an YMC ODS column （250 mm × 4.6 mm i. d. , 5 μm） with a mobile phase consisting of 10 mmol/L potassium dihydrogen phosphate （adjusted to pH 3. 0 with phosphoric acid） and acetonitrile （60 ： 40, V/V） at a flow rate of 1. 0 mL/min. Quantification was performed by fluorescence detection at an excitation wavelength of 270 nm and an emission wavelength of 390 nm. A single oral dose of 8mg candesartan cilexetil tablet was given to 20 healthy volunteers. The candesartan concentrations in serum were determined by the above-mentioned method. The main pharmacokinetic parameters were detected and calculated. Results The linear range of candesartan concentration was 1.01 to 202 μg/L in serum with a correlation coefficient （r） of 0. 999 7. The relative standard deviations （RSDs） of intra-day and inter-day assays were 5.22% -9. 14% and 3.58% - 10. 39%, respectively. Conclusions This method proved to be sensitive and reproducible for pharmacokinetic studies of candesartan cilexetil in healthy volunteers after a single oral administration （8 mg）.