Simultaneous quantitation of dexmedetomidine and glucuronide metabolites (G‐Dex‐1 and G‐Dex‐2) in human plasma utilizing liquid chromatography with tandem mass spectrometric detection

Abstract

Dexmedetomidine (Dex) (Precedex™) is a novel lipophilic imidazole derivative with a high affinity for alpha‐2 adrenergic receptors, which exhibits sedative, analgesic‐sparing, and sympatholytic properties. The pharmacological effects and therapeutic benefits of this drug have drawn continued interest from the medical community. Here we report a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method to simultaneously measure the concentrations of dexmedetomidine and its glucoronide metabolites, G‐Dex‐1 and G‐Dex‐2, in human plasma samples. A solid‐phase extraction method was developed to effectively extract Dex, G‐Dex‐1, and G‐Dex‐2 from plasma matrices. An isocratic chromatographic method was developed to achieve baseline separation of G‐Dex‐1 and G‐Dex‐2. The linear dynamic range evaluated was 19.08–1908.56 pg/mL for Dex, 65.17–6518.17 pg/mL for G‐Dex‐1, and 29.42–2943.28 pg/mL for G‐Dex‐2. The linear correlation coefficient (r) ranged from 0.9944–0.9979 for Dex, from 0.9966–0.9984 for G‐Dex‐1, and from 0.9939–0.9966 for G‐Dex‐2. The intra‐assay coefficient of variation (CV) was between 2.5–12.5% for Dex, between 5.2–11.0% for G‐Dex‐1, and between 3.5–12.1% for G‐Dex‐2. The inter‐assay precision of QC samples give % CV ranges from 6.5–9.3% for Dex, from 7.1–10.6% for G‐Dex‐1, and from 8.2–10.2% for G‐Dex‐2. The inter‐assay accuracies ranged from 102.0–109.3% for Dex, from 95.4–105.6% for G‐Dex‐1, and from 98.7–115.0% for G‐Dex‐2. Copyright © 2004 John Wiley & Sons, Ltd.