Determination of Hydrochlorothiazide in Human Plasma by LC-MS/MS and Its Pharmacokinetics

A LC-MS/MS method was established for the determination of hydrochlorothiazide in human plasma. Pharmacokinetics after oral administration of candesartan cilexetil hydrochlorothiazide tablets in 20 healthy volunteers was investigated.The calibration curve of hydrochlorothiazide was linear in the concentration range of 1-200ng/ml.The pharmacokinetic parameters of single oral doses of 12.5 and 25mg were as follows:C_(max)(74.14±15.04)and(125.57±23.47)ng/ml,t_(max)(1.85±0.53)and(2.20±0.59)h,t_(1/2)β(11.57±2.39)and(10.93±1.71)h,AUC_(0→48h)(470.0±90.7)and(794.7±182.6)h·ng·ml~(-1),respectively.The pharmacokinetic parameters at steady state were t_(max)(1.83±0.25)h,C_(max)~(ss)(80.21±17.98)ng/ml,C_(min)~(ss)(3.72±1.79)ng/ml,c_(av)(19.37±3.20)ng/ml,AUC_(0→48h)(484.90±76.89)h·ng·ml~(-1),respectively.