Rapid quantification of lisinopril in human plasma by liquid chromatography/tandem mass spectrometry

Abstract An assay based on protein precipitation and liquid chromatography/tandem mass spectrometry (LC‐MS/MS) has been developed and validated for the quantitative analysis of lisinopril in human plasma. After the addition of enalaprilat as internal standard (IS), plasma samples were prepared by one‐step protein precipitation using perchloric acid followed by an isocratic elution with 10 m m ammonium acetate buffer (pH adjusted to 5.0 with acetic acid)–methanol (70:30, v/v) on a Phenomenex Luna 5µC 18 (2) column. Detection was performed on a triple‐quadrupole mass spectrometer utilizing an electrospray ionization (ESI) interface operating in positive ion and selected reaction monitoring (SRM) mode with the precursor to product ion transitions m / z 406→246 for lisinopril and m / z 349→206 for enalaprilat. Calibration curves of lisinopril in human plasma were linear ( r = 0.9973−0.9998) over the concentration range 2–200 ng/mL with acceptable accuracy and precision. The limit of detection and lower limit of quantification in human plasma were 1 and 2 ng/mL, respectively. The validated LC‐MS/MS method has been successfully applied to a preliminary pharmacokinetic study of lisinopril in Chinese healthy male volunteers. Copyright © 2007 John Wiley & Sons, Ltd.