Improved high-performance liquid chromatographic assay for the stereoselective determination of mexiletine in plasma.
A simple and sensitive high-performance liquid chromatographic procedure for resolution of mexiletine enantiomers has been developed. Proteins from plasma samples containing RS-mexiletine were precipitated with a mixture of barium hydroxide and zinc sulphate before extraction under alkaline conditions with diethyl ether. Organic extracts were evaporated to dryness, and the residues reconstituted with 0.03 M hydrochloric acid (20 microliters). Derivatization with o-phthalaldehyde N-acetyl-L-cysteine reagent was performed after alkalinization with 0.1 M sodium borate. An aliquot of the resulting solution was injected onto a reversed-phase C18 column and resolution of mexiletine diastereoisomeric derivatives was achieved with a mobile phase consisting of methanol-50 mM sodium acetate (65:35), at a flow-rate of 1 ml/min. The retention times of S-(+)- and R-(-)-mexiletine diastereoisomeric peaks were 14 and 15 min, respectively. Product elution was monitored by fluorescence detection using excitation and emission wavelengths fixed at 350 and 445 nm, respectively. Calibration curves were linear over the concentration range 2.5-500 ng/ml for each enantiomer (r greater than 0.99). The assay is shown to be suitable for pharmacokinetic studies after administration of a single oral dose of 200 mg of RS-mexiletine hydrochloride to healthy volunteers.
Abolfathi
Z
Z
Institut de Cardiologie de Québec, Hôpital Laval, Ste-Foy, Canada.
Bélanger
P M
PM
Gilbert
M
M
Rouleau
J R
JR
Turgeon
J
J
D000284:Administration, Oral; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005453:Fluorescence; D006801:Humans; D008801:Mexiletine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D013237:Stereoisomerism
D008801:Mexiletine