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 me xiletine enantiomers using a new fluorogenic derivatization reagent, 2 -anthroyl chloride. The reagent was synthesized and utilized for the f luorescent detection (excitation at 270 nm, emission at 400 nm) of mex iletine enantiomers as their N-anthroyl derivatives on a Pirkle phenyl glycine 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 prelimi nary pharmacokinetic study, 200 mg of racemic mexiletine hydrochloride were administered orally to two healthy volunteers. Serum samples wer e collected at timed intervals over 48 h. The terminal elimination hal f-lives determined for total R(-)- and S(+)-mexiletine were 10.9 and 1 1.5 h, respectively. The serum free fractions for R(-)- and S(+)-mexil etine were found to be 0.56 and 0.53, respectively.