A Liquid Chromatography/Tandem Mass Spectrometric Method for Determination of Captopril in Human Plasma: Application to a Bioequivalence Study

A simple, rapid and sensitive ultra-performance liquid chromatography/positive ion electrospray tandem mass spectrometric method was developed and validated for the quantification of captopril in human plasma. Following plasma protein precipitation, the analyte and internal standard Rosuvastatin were separated by ultra-performance liquid chromatography using a gradient mode mobile phase on a reversed-phase column and analyzed by mass spectrometry in the multiple reaction monitoring mode (MRM) using the respective [MRH]R ions, m/z 218.09/116.16 for captopril and m/z 482.2/ 258.17 for the internal standard. The method exhibited a linear dynamic range of 10–2000 ng/mL for captopril in human plasma. The lower limit of quantification was 10 ng/mL with a relative standard deviation of less than 6%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A total run time of 3 minutes for each sample made it possible to analyze more than 20 human plasma samples per one hour. The validated method has been successfully applied to analyze human plasma samples in a bioequivalence study of captopril after oral administration of 50 mg captopril tablet to 24 healthy subjects.