High-performance liquid chromatographic analysis using a highly sensitive fluorogenic reagent, 2-anthroyl chloride, and stereoselective determination of the enantiomers of mexiletine in human serum.
A stereoselective and highly sensitive HPLC assay was developed for mexiletine enantiomers using a new fluorogenic derivatization reagent, 2-anthroyl chloride. The reagent was synthesized and utilized for the fluorescent detection (excitation at 270 nm, emission at 400 nm) of mexiletine enantiomers as their N-anthroyl derivatives on a Pirkle phenylglycine ionic HPLC column. The assay had a lower limit of quantitation at 2.5 ng/ml with a limit of detection measured at 0.5 ng/ml for each enantiomer in serum with a signal-to-noise ratio of 5:1. In a preliminary pharmacokinetic study, 200 mg of racemic mexiletine hydrochloride were administered orally to two healthy volunteers. Serum samples were collected at timed intervals over 48 h. The terminal elimination half-lives determined for total R(-)- and S(+)-mexiletine were 10.9 and 11.5 h, respectively. The serum free fractions for R(-)- and S(+)-mexiletine were found to be 0.56 and 0.53, respectively.
Kowk
D K
DK
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Igwemezie
L
L
Kerr
C R
CR
McErlane
K M
KM
D000873:Anthracenes / Q000737:chemistry*; D002138:Calibration; D002712:Chlorides / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D008297:Male; D008801:Mexiletine / Q000097:blood* / Q000493:pharmacokinetics; D012016:Reference Values; D015203:Reproducibility of Results; D013237:Stereoisomerism
C092649:2-anthroyl chloride; D000873:Anthracenes; D002712:Chlorides; D005456:Fluorescent Dyes; D008801:Mexiletine