title: High-performance liquid chromatographic determination of mexiletine enantiomers in plasma using direct and indirect enantioselective separations.
abstract: Two methods were developed for the determination of mexiletine enantiomers in plasma samples suitable for studies on the stereoselective disposition of this drug. Both methods used fluorescence detection to improve sensitivity and selectivity. The direct enantioselective separation was based on the chiral resolution of mexiletine-2-naphthamide derivatives on a Chiralcel OJ column. The calibration curves were linear over the concentration range 50-500 ng/ml for each enantiomer; therefore the method can be used only for therapeutic monitoring, drug interaction and multiple dose pharmacokinetic studies. The indirect method was based on the formation of diastereomers using o-phthaldialdehyde and N-acetyl-L-cysteine reagents. The diastereomers were resolved on a reversed-phase RP-18 column. The method proved to be suitable for single or multiple dose pharmacokinetic studies based on the low quantification limit (1 ng/ml) and the broader linear range (1-1000 ng/ml) obtained.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão, Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: V L
authors.initials: VL
authors.lastname: Lanchote
authors.forename: P S
authors.initials: PS
authors.lastname: Bonato
authors.forename: S A
authors.initials: SA
authors.lastname: Dreossi
authors.forename: P V
authors.initials: PV
authors.lastname: Gonçalves
authors.forename: E J
authors.initials: EJ
authors.lastname: Cesarino
authors.forename: C
authors.initials: C
authors.lastname: Bertucci
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002214:Capsules; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002940:Circadian Rhythm; D003545:Cysteine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry; D016014:Linear Models; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D009281:Naphthalenes / Q000737:chemistry; D009994:Osmolar Concentration; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D009764:o-Phthalaldehyde / Q000737:chemistry
chemical_list: D000889:Anti-Arrhythmia Agents; D002214:Capsules; D007202:Indicators and Reagents; D009281:Naphthalenes; D008801:Mexiletine; C104664:2-naphthoyl chloride; D009764:o-Phthalaldehyde; D003545:Cysteine