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

摘要

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 x 250 mm, 5 mu m, 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 degrees C. The detection was carried out at 261 nm for DL-3-phenyllactic acid and DL-O-acetyl-3-phenyl lactic 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. (C) 2007 Elsevier B.V. All rights reserved.