Quantification of zolpidem in human plasma by liquid chromatography–electrospray ionization tandem mass spectrometry

A simple and robust method for quantification of zolpidem in human plasma has been established using liquid chromatography–electrospray ionization tandem mass spectrometry (LC‐ESI MS/MS). Es‐citalopram was used as an internal standard. Zolpidem and internal standard in plasma sample were extracted using solid‐phase extraction cartridges (Oasis HLB, 1 cm 3 /30 mg). The samples were injected into a C 8 reversed‐phase column and the mobile phase used was acetonitrile–ammonium acetate (pH 4.6; 10 mm) (80:20, v/v) at a flow rate of 0.7 mL/min. Using MS/MS in the selected reaction‐monitoring (SRM) mode, zolpidem and Es‐citalopram were detected without any interference from human plasma matrix. Zolpidem produced a protonated precursor ion ([M+H] + ) at m/z 308.1 and a corresponding product ion at m/z 235.1. The internal standard produced a protonated precursor ion ([M+H] + ) at m/z 325.1 and a corresponding product ion at m/z 262.1. Detection of zolpidem in human plasma by the LC‐ESI MS/MS method was accurate and precise with a quantification limit of 2.5 ng/mL. The proposed method was validated in the linear range 2.5–300 ng/mL. Reproducibility, recovery and stability of the method were evaluated. The method has been successfully applied to bioequivalence studies of zolpidem. Copyright © 2005 John Wiley & Sons, Ltd.