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

Abstract

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 cm3/30 mg). The samples were injected into a C8 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.

In vitro metabolism of tiletamine, zolazepam and nonbenzodiazepine sedatives: Identification of target metabolites for equine doping control

“…The MS/MS fragmentation of zolpidem and its most abundant in vitro mono‐oxygenated metabolite (M1) are rationalized in Figure 3. Major peaks in both spectra related to neutral losses from the amide containing side‐chain, which is consistent with the previously reported MS/MS spectra of zolpidem 10. The same neutral MS/MS losses were also identified in the spectra of the carboxy (M5) and in two of the remaining mono‐oxygenated metabolites (M2 and M3), suggesting that each of these oxidations occurred on the aromatic rings rather than the amide‐containing side chain.…”

Issues Affecting Interpretation: Stability and Artefacts

“…samples. Bhatt et al (2006) observed no instability of zolpidem in samples stored for 60 days at 70°C; mean percent changes <13% were estimated from plasma stored at room temperature and from processed samples in the autosampler (5°C) after 6 and 24 hours, respectively. A comprehensive overview on the stability of antidepressants, neuroleptics, antiepileptics and cardiovascular drugs is given by Peters (2007).…”

Multiobjective Optimization Approach in Evaluation of Chromatographic Behaviour of Zolpidem Tartrate and Its Degradation Products

“…The literature search revealed several reported analytical approaches for the determination of zolpidem in biological materials including liquid chromatography with fluorescence [4][5][6][7], ultraviolet [8,9] or mass detection [10][11][12][13], gas chromatography [14][15][16][17] and capillary electrophoresis [18]. Determination of zolpidem tartrate in the presence of zolpacid and dimethylamine was performed by HPTLC and HPLC methods [19].…”