Development and validation of HPLC method for the resolution of drug intermediates: dl-3-Phenyllactic acid, dl-O-acetyl-3-phenyllactic acid and (±)-mexiletine acetamide enantiomers

Sensitive and specific, high-performance liquid chromatography (HPLC) methods have been developed and validated for linearity, accuracy and precision for the quantification of dl-3-phenyllactic acid, dl-O-acetyl-3-phenyllactic acid and (±)-mexiletine acetamide enantiomers. Chromatographic separations were performed on a Chiralcel OJ-H column (0.46 mm × 250 mm, 5 μm, Daicel Chemical Industries, Japan) based on cellulose tris-(4-methyl benzoate) chiral stationary phase. The mobile phase consists of hexane and isopropanol (IPA) in the ratio of 90:10 containing 0.1% trifluoroacetic acid (in case of dl-3-phenyllactic acid and dl-O-acetyl-3-phenyllactic acid) and hexane and IPA (95:5) containing 0.1% triethylamine (in case of (±)-mexiletine acetamide) and the flow rate was set at 0.5 ml/min at 25 °C. The detection was carried out at 261 nm for dl-3-phenyllactic acid and dl-O-acetyl-3-phenyllactic acid and at 254 nm for (±)-mexiletine acetamide. The developed methods were utilized for monitoring the progress of lipase catalyzed enantioselective synthesis of O-acetyl-3-phenyllactic acid and mexiletine acetamide from dl-3-phenyllactic acid and (±)-mexiletine, respectively.