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Enantioselective determination of the hydroxylated metabolites of mexiletine in human plasma
Author(s) -
Lanchote Vera Lúcia,
Bonato Pierina Sueli,
Cesarino Evandro José,
Ali Mere Yussif,
Cavani Silvia Regina,
Santos Jorge,
Bertucci Carlo
Publication year - 1997
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1997)9:8<732::aid-chir4>3.0.co;2-7
Subject(s) - chemistry , mexiletine , enantioselective synthesis , human plasma , chromatography , plasma , pharmacology , stereochemistry , organic chemistry , medicine , catalysis , physics , quantum mechanics
Pre‐column derivatization with o‐phthaldialdehyde and N‐acetyl‐l‐cysteine was used for liquid‐chromatographic diastereomeric resolution of p‐hydroxymexiletine (PHM) and hydroxymethylmexiletine (HMM), metabolites of mexiletine formed by aromatic and aliphatic hydroxylation, respectively. The resulting diastereomeric derivatives were resolved on a C 18 column and monitored by fluorescence detection. The diastereomeric elution order for both metabolites was determined on the basis of the circular dichroism spectra of each eluted fraction. Plasma samples (500 μl) showed recoveries greater than 75% for both the metabolites. Calibration curves in plasma samples were linear over the concentration ranges 10–500 and 20–1,000 ng/ml for each enantiomer of PHM and HMM, respectively. The limits of quantitation were found to be 10.0 and 5.0 ng/ml for both enantiomers of PHM and HMM. The within‐day and between‐day coefficients of variation were less than 10%. The assay was shown to be suitable for a pharmacokinetic study performed in a patient with ventricular arrhythmias following the short‐term oral treatment of 200 mg t.i.d. of racemic mexiletine hydrochloride. Chirality 9:732–738, 1997. © 1997 Wiley‐Liss, Inc.