title: The development and cross-validation of methods based on radioimmunoassay and LC/MS-MS for the quantification of the class III antiarrhythmic agent, MK-0499, in human plasma and urine.
abstract: An analytical method based on radioimmunoassay (RIA) has been developed for the determination of the antiarrhythmic agent, MK-0499, in plasma and urine. Owing to the potency of the drug, the specificity of this assay in human plasma could not be adequately determined using conventional RIA procedures. A highly specific procedure, based on LC/MS-MS, was developed to cross-validate the RIA. The lower quantifiable limits of the RIA and LC/MS-MS-based methods were 0.05 and 0.013 ng ml-1, respectively. Cross-validation data, compared using paired student's t-test regression analysis, showed excellent correlation between methods. The mass spectrometric assay was also used to simultaneously measure plasma concentrations of unlabeled and 14C-labeled MK-0499 following administration of the drug at high specific activity to volunteers.
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Gilbert
authors.forename: T F
authors.initials: TF
authors.lastname: Greber
authors.forename: J D
authors.initials: JD
authors.lastname: Ellis
authors.forename: A
authors.initials: A
authors.lastname: Barrish
authors.forename: T V
authors.initials: TV
authors.lastname: Olah
authors.forename: C
authors.initials: C
authors.lastname: Fernández-Metzler
authors.forename: A S
authors.initials: AS
authors.lastname: Yuan
authors.forename: C J
authors.initials: CJ
authors.lastname: Burke
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000032:analysis* / Q000097:blood / Q000652:urine; D000918:Antibody Specificity; D001578:Benzopyrans / Q000032:analysis* / Q000097:blood / Q000652:urine; D002138:Calibration; D002853:Chromatography, Liquid; D005260:Female; D005615:Freezing; D006241:Haptens / Q000737:chemistry; D006801:Humans; D007202:Indicators and Reagents; D007553:Isotope Labeling; D013058:Mass Spectrometry; D010880:Piperidines / Q000032:analysis* / Q000097:blood / Q000652:urine; D011786:Quality Control; D011817:Rabbits; D011863:Radioimmunoassay; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000889:Anti-Arrhythmia Agents; D001578:Benzopyrans; D006241:Haptens; D007202:Indicators and Reagents; D010880:Piperidines; C087257:L 706000