title: Simultaneous determination of ebastine and its three metabolites in plasma using liquid chromatography-tandem mass spectrometry.
abstract: We developed a method for determining ebastine, a new generation of antihistamines, and its three metabolites (hydroxyebastine, carebastine and desalkylebastine) in plasma simultaneously using LC/MS/MS. Four compounds and terfenadine, an internal standard, were extracted from plasma using a mixture of diethylether and dichloromethane in the presence of 1 M HCl. After drying the organic layer, the residue was reconstituted in mobile phase (acetonitrile:5 mM ammonium acetate, 50:50, v/v) and injected onto a reversed-phase C(18) column. The isocratic mobile phase was eluted at 0.2 ml/min. The ion transitions monitored in multiple reaction-monitoring mode were m/z 470.7-->167.1, 486.7-->167.1, 500.6-->167.1, 268.4-->167.1 and 472.7-->436.0 for ebastine, hydroxyebastine, carebastine, desalkylebastine and terfenadine, respectively. The coefficient of variation of the assay precision was less than 12.5%, and the accuracy exceeded 88%. The limit of detection was 0.5 ng/ml for desalkylebastine; 0.2 ng/ml for ebastine, hydroxyebastine and carebastine, respectively. This method was used to measure the plasma concentration of ebastine and its three metabolites from healthy subjects after a single 20 mg oral dose of ebastine. This analytic method is a very simple, sensitive, and accurate to determine the pharmacokinetic profiles of ebastine including its metabolites.
authors.affiliation: Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan, South Korea.
authors.forename: Wonku
authors.initials: W
authors.lastname: Kang
authors.forename: Kwang-Hyeon
authors.initials: KH
authors.lastname: Liu
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Ryu
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
mesh_terms: D002090:Butyrophenones / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D006634:Histamine H1 Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D010880:Piperidines / Q000097:blood* / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity
chemical_list: D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; C058249:ebastine