Study of Pharmacokinetics and Bioequivalence of Telmisartan in Human Plasma by HPLC-MS Method

Objective:To establish an accurate and sensitive HPLC-MS method for the determination of telmisar- tan in plasma and to evaluate its pharmacokinetic parameters and bioequivalence in healthy volunteers.Method:A single oral dose of 40 mg telmisartan test or reference tablets was given to 20 healthy volunteers in two-way cross -over design.The plasma sample were collected at predetermined time points after the administration,which were extracted by acetonitrile.The plasma concentration of telmisartan were determined by HPLC-MS using Zorbax SB -C_(18)(3.5μm,3.0mm×100mm),acetonitrile-0.02mol·L~(-1)NH_4Ac(28:72)as mobile phase,with positive ion SIM detection of telmisartan([MH]~+,m/z=515.3)using kadishatan([MH]~+,m/z=423.3)as the internal reference.Results:The limit of detection of telmisartan was 0.5ng·mL~(-1)and a good linearity was obtained in the range of 2-500ng·mL~(-1) with the established HPLC-MS method.The relative standard deviation of within-day and between-day determination were less than 10%.The main pharmacokinetic parameters after a single oral dose of 40 mg telmisartan of the test or reference tablets were as follows:C_(max)(μg·L~(-1))220.70±95.80 and 233.11± 105.52,AUC_(0-96)(μg·h·L~(-1))1908.54±650.43 and 1986.26±553.24,t_(1/2)(h)24.1±4.2 and 24.8±3.8, T_(max)(h)1.8±0.6 and 1.7±0.7,respectively;the relative bioavailabity of the test to reference tablets was 95.6% ±6.4%.Conclusion:The established HPLC-MS method was shown to be sensitive and accurate.The statistic results shown that test and reference tablets of telmisartan were bioequivalent.