High-performance liquid chromatographic method for resolving the enantiomers of mexiletine and two major metabolites isolated from microbial fermentation media.

摘要: Abstract (±)-Mexiletine is a class Ib antiarrhythmic drug useful in the treatment of premature ventricular contractions. It predominantly metabolized by liver with less than 15% being excreted urine as unchanged drug. p-Hydroxymexiletine (PHM) and hydroxymethylmexiletine (HMM) are two major mammalian metabolites. The purpose our study was to develop stereospecific high-performance liquid chromatographic (HPLC) method determine whether fungus, Cunninghamella echinulata (UAMH 4145), able biosynthesize these same metabolites from substrate (±)-mexiletine. Furthermore, it desirable ascertain metabolism mexiletine stereoselective. requires pre-column derivatization S-(+)-1-(1-naphthyl)ethyl isocyanate (NEIC) followed normal-phase HPLC. Mexiletine, PHM, HMM (±)-1-(4-hydroxyphenoxy)-3-isopropylaminopropan-2-ol (internal standard) were extracted microbial broth using volumes diethyl ether after basifying sodium carbonate. combined extracts evaporated dryness, gentle stream nitrogen, reconstituted 0.3 ml chloroform which added 0.075 NEIC (0.1%, v/v, chloroform). This solution immediately dryness under nitrogen stream. residue 0.220 0.030 n-butylamine (0.33%, chloroform) injected into HPLC system.