title: Analytical method development for the simultaneous quantitation of dexmedetomidine and three potential metabolites in plasma.
abstract: Dexmedetomidine, a novel alpha 2-adrenergic receptor agonist, is being developed as an anesthetic adjunct for perioperative use. An assay method has been developed for the sensitive quantitation of dexmedetomidine and three metabolites in plasma: MPV-1305, MPV-1306 and MPV-1709. The method involves solid-phase extraction (C18 cartridge) of dexmedetomidine and metabolites followed by a two-step derivatization. The first step utilized BF3-MeOH to simultaneously mask a primary alcohol in MPV-1305 and a carboxylic acid in MPV-1306. The second step applied PFB-Cl to derivatize the imidazole ring for sensitive detection of these compounds by GC-negative chemical ionization MS at pg/ml concentrations. MPV-1709 was not derivatized in the process and was detected by GC-positive chemical ionization MS. Optimization of extraction and derivatization is discussed. The method is suitable for quantitation of dexmedetomidine, MPV-1305, MPV-1306 and MPV-1709 over concentration ranges of 0.1, 40, 0.5-100, 0.5-100 and 1.0-500 ng/ml, respectively. The method showed excellent specificity, linearity and sensitivity and is useful for profiling the pharmacokinetic disposition of these compounds.
authors.affiliation: Abbott Laboratories, IL 60064-3500, USA.
authors.forename: Y H
authors.initials: YH
authors.lastname: Hui
authors.forename: K C
authors.initials: KC
authors.lastname: Marsh
authors.forename: S
authors.initials: S
authors.lastname: Menacherry
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D002940:Circadian Rhythm; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D007093:Imidazoles / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D020926:Medetomidine; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013696:Temperature; D013997:Time Factors
chemical_list: D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D020926:Medetomidine