title: Enantioselective analysis of disopyramide and mono-N-dealkyldisopyramide in plasma and urine by high-performance liquid chromatography on an amylose-derived chiral stationary phase.
abstract: An enantioselective high-performance liquid chromatography method was developed for the simultaneous determination of disopyramide (DP) and mono-N-dealkyldisopyramide (MND) enantiomers in plasma and urine. The drugs were extracted from plasma samples by liquid-liquid extraction with dichloromethane after protein precipitation with trichloroacetic acid; the urine samples were processed by liquid-liquid extraction with dichloromethane. The enantiomers were resolved on a Chiralpak AD column using hexane-ethanol (91:9, v/v) plus 0.1% diethylamine as the mobile phase and monitored at 270 nm. Under these conditions the enantiomeric fractions of the drug and of its metabolite were analyzed within 20 min. The extraction procedure was efficient in removing endogenous interferents and low values for the relative standard deviations were demonstrated for both within-day and between-day assays. The method described in this paper allows the determination of DP and MND enantiomers at plasma levels as low as 12.5 ng/ml and can be used in clinical pharmacokinetic studies.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Bortocan
authors.forename: V L
authors.initials: VL
authors.lastname: Lanchote
authors.forename: E J
authors.initials: EJ
authors.lastname: Cesarino
authors.forename: P S
authors.initials: PS
authors.lastname: Bonato
mesh_terms: D000688:Amylose / Q000737:chemistry*; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004206:Disopyramide / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D000889:Anti-Arrhythmia Agents; D000688:Amylose; D004206:Disopyramide