离子对液相色谱法测定人血浆中替米沙坦的浓度及药动学研究

Ion-pair HPLC determination and pharmacokinetic study of telmisartan in human plasma

目的建立测定人血浆中替米沙坦浓度的高效液相色谱方法,并用该法研究替米沙坦片在健康人体内的药动学.方法色谱柱为Shim-pack VP-ODS(150mm×4.6mm),流动相为乙腈-0.05%戊磺酸钠-0.05 mol·L-1磷酸二氢钾(50:25:25),荧光检测,激发波长为305nm,发射波长为365nm.结果血浆样品在3.05～610.0μg·L-1内线性相关(r=0.9999,n=5).平均绝对回收率为85.1%(RSD=1.63%),相对回收率大于95.0%,日间和日内相对标准差小于10.0%.10名男性健康志愿者单次口服80mg替米沙坦片后,其药代动力学参数分别为:t1/2(19.8±5.66)h,cmax(310.7±91.6)μg·L-1,tmax(1.01±0.40)h.结论此方法准确,灵敏,适于体内药物分析;药动学参数为临床合理用药提供理论依据.

OBJECTIVE To establish an HPLC method for the determination of telmisartan concentration in plasma, and to investigate the pharmacokinetics of telmisartan in Chinese healthy volunteers. METHODS The chromatographic separation was achieved on a Shim-pack VP-ODS （ 150mm × 4.6mm）, the mobile phase was consisted of acetonitrile - 0.05% pentanesulfonate - 0.05 mol·L^-1 potassium dihydrogen phosphate （50：25：25 ）, fluorescence detection （excitation at 305 nm, emission at 365 nm） was used for quantitation. RESULTS A good linearity was obtained from 3.05 to 610.0 μg·L^-1 （ r = 0. 9999, n = 5 ）. The mean recovery of plasma extraction was 85.1% （ RSD = 1.7% ）, relative recovery was more than 95%, the within-day and between-day RSD were less than 10.0%. The pharamacokinetic analysis of telmisartan after oral administration of 80 mg telmisartan tablets was studied. Its pharmaco- kinetic parameters were as follow： t1/2（19.8 ±5.66） h, Cmax（310.7 ±91.6）μg·L^-1, tmax（1.01±0.40） h. CONCLUSION The method is rapid, simple and accurate. The pharmacokinetics of telmisartan in human provided a useful index for clinical trial.