title: Simultaneous determination of disopyramide and mono-N-dealkyldisopyramide enantiomers in plasma and urine by use of a chiral cellulose-derivative column.
abstract: This assay allows simultaneous determination of the enantiomers of both disopyramide and its active metabolite, mono-N-dealkyldisopyramide, in 1 mL of plasma or 0.1 mL of urine within approximately 35 min by HPLC with a chiral cellulose-derivative column and ultraviolet detection. Recoveries for the analytes and the internal standard (racemic verapamil) with an extraction from alkalinized plasma or urine into diethyl ether were greater than 90%. Intra- and interassay CVs for disopyramide enantiomers were less than 5.5% at 2.5 mg/L in plasma and less than 6.5% at 25 mg/L in urine; for mono-N-dealkyldisopyramide enantiomers they were less than 6.3% and less than 8.9%, respectively. Intra- and interassay relative errors for determining these analytes in plasma and urine at 2.5 and 25 mg/L, respectively, ranged from -5.9% to +2.5%. The calibration curves for the respective analytes were linear (r = 0.995 or greater, P less than 0.01) from 0.025 to 5.0 mg/L in plasma and from 0.5 to 10 mg/L in urine. The lower detection limits (signal-to-noise ratio of 3) for S(+)-disopyramide and the other analytes were 0.010 and 0.025 mg/L, respectively. We evaluated clinical applicability of this method by determining steady-state plasma concentrations and urinary excretions of the respective analytes in a pediatric patient being treated with racemic disopyramide.
authors.affiliation: Division of Geriatric Health and Nutrition, National Institute of Health and Nutrition, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Echizen
authors.forename: K
authors.initials: K
authors.lastname: Ochiai
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Chiba
authors.forename: T
authors.initials: T
authors.lastname: Ishizaki
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000032:analysis* / Q000493:pharmacokinetics; D002482:Cellulose / Q000031:analogs & derivatives; D002851:Chromatography, High Pressure Liquid; D004206:Disopyramide / Q000031:analogs & derivatives* / Q000032:analysis* / Q000493:pharmacokinetics; D006801:Humans; D008657:Metabolic Clearance Rate; D008991:Monitoring, Physiologic; D013237:Stereoisomerism
chemical_list: D000889:Anti-Arrhythmia Agents; C030438:4-(isopropylamino)-2-(2-pyridyl)-2-phenylbutyramide; D002482:Cellulose; D004206:Disopyramide