Fast chiral chromatographic method development and validation for the quantitation of eszopiclone in human plasma using LC/MS/MS

Abstract

Traditional chiral chromatographic separation method development is time consuming even for an experienced chromatographer. This paper describes the application of computer software ACD Lab ® to facilitate the development of chiral separation for the quantitation of eszopiclone using LC–MS/MS technology. Assisted by ACD/Chrom Manager and LC Simulator software, the optimal chiral chromatographic development was completed within hours. The baseline chiral separation was achieved with a total cycle time of 3 min. For sample extraction method development, a Waters Oasis ® Sorbent Selection Plate containing four different sorbents was utilized. Optimal conditions were determined using a single plate under various load, wash and elution conditions. This was followed by a GLP validation which demonstrated excellent intra- and inter-day accuracy and precision for the quantitation of eszopiclone in human plasma at 1.00–100 ng/mL range using LC/MS/MS technology. This method was utilized to support multiple clinic bioequivalence studies.