Study on the pharmacokinetic in vivo of captopril in human plasma with LC-MS/MS

Objective:To establish an LC-MS/MS method for determination of captopril in human plasma and to study the pharmacokinetics for two preparations in healthy volunteers.Methods:Using p-bromophenacyl bromide (p-BPB)as a stabilizer and derivative reagent,the derivates were determined by LC-MS/MS using risperidone as the internal standard.Separation was obtained on Alltima C_(18)(100mm×2.1mm,3.0 μm)column with the mo- bile phase of acetonitrile-0.025% formic acid solution(60:40)at the flow rate of 0.2 mL·min~(-1).Atmospheric pressure chemical ionization source was applied and operated in positive ion mode.Selected reaction monitoring mode with transitions of m/z 414.1→210.6 and m/z 411.3→191.1 was adopted to quantify captopril derivate and internal standard,respectively.Results:The calibration curve of captopril was linear in the range of 1.0-748.0 ng ·mL~(-1)and detection limit was 1.0 ng·mL~(-1).The inter-and intra-day precision(RSD)were below 5.8%. The recovery of the method was(103.5±5.8)%.To study the pharmacokinetics and the relative bioavailability of two preparations of captopril,tablets were given to 18 healthy volunteers.The pharmacokinetic parameters were re- ported:T_(max)(h)were 0.72±0.19 and 0.68±0.14,C_(max)(ng·mL~(-1))were 343.4±132.3 and 333.6±94.6,T_(1/2) (h)were 2.07±0.65 and 2.07±0.69,AUC_(0-t)(ng·h·mL~(-1))were 442.5±95.6 and 424.9±78.3.Conclu- sion:This method is convenient,sensitive,specific and suitable for pharmacokinetics and relative bioavailability study.