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.
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.
Department of Drug Analysis, Abbott Laboratories, Abbott Park, IL 60064, USA. Qin.Ji@abbott.com
Qin C
QC
Ji
Julie Y
JY
Zhou
R John
RJ
Gonzales
Eric M
EM
Gage
Tawakol A
TA
El-Shourbagy
D002138:Calibration; D002853:Chromatography, Liquid; D020927:Dexmedetomidine / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D005615:Freezing; D020719:Glucuronides / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D015394:Molecular Structure; D012015:Reference Standards; D012680:Sensitivity and Specificity; D013048:Specimen Handling; D013696:Temperature
D020719:Glucuronides; D020927:Dexmedetomidine