LC-MS/MS determination of hydrochlorothiazide in human plasma and study its pharmacokinetics

Objective:To establish a method for determination of hydrochlorothiazide in human plasma and study its pharmacokinetics by LC-MS/MS.Methods:20 Healthy volunteers received hydrochlorothiazide tablets(single doses, multidose),drug concentrations in plasma were determined.Results:Pharmacokinetic parameters of hydrochlorothiaz- ide after single oral doses(12.5,25mg)were as follow:T_(1/2β):(13.57±2.39),(10.93±1.71)h;T_(max):(1.85± 0.53),(2.20±0.59)h;C_(max):(74.14±15.04),(125.57±23.47)μg·L~(-1);AUC_(0-48):(470.0±90.7),(794.7± 182.6)μg·h·L~(-1).The essential pharmacokinetic parameters after oral muhidose(12.5mg,qd)were as follow: T_(max)~(SS)(1.83±0.25)h,C_(max)~(SS):(80.21±17.98)μg·L~(-1),C_(min)~(SS):(3.72±1.79)μg·L~(-1),C_(av):(19.37±3.20)μg· L~(-1),AUC_(0-48)~(SS):(464.90±76.89)μg·h·L~(-1).Conclusion:The method is sensitive;the results were accurate;a two -compartment open pharmaeokinetic model is adapted to hydroehlorothiazide plasma concentration-time data analy- sis;the main pharmacokinetic parameters are similar to those reported domestic and abroad.