Pharmaceutical drug products are structurally diverse with more than 70% being chiral in nature. Determining the chiral purity is crucial as each enantiomer either potentially exhibits the same physico-chemical and therapeutic properties or one of the other enantiomers might produce different therapeutic or adverse effects due to different pharmacological or toxicological behavior. For evaluating the safety and efficacy profile of a drug the initial step is to separate the enantiomeric forms and determine the chiral purity. Traditional chiral separation procedures are complex, with limited high throughput capabilities. Ultra-Performance Convergent Chromatography is an innovative emerging analytical technique that merges the resolution capabilities of super critical fluid and ultra performance liquid chromatography (UPLC) and provide the advantages of both gas chromatography (GC) and UPLC.<br/>            The FDA’s “Critical Path” initiative is a framework to help develop and implement new analytical tools and methods for complex drug substances in support of novel approaches for the evaluation of the product quality of complex drug products. The primary goal of this study was to develop efficient convergence methods to enantiomerically separate different drugs as part of a ‘critical path” study, and to understand how this innovative technique can effectively address regulatory issues and challenges for demonstrating the sameness of the active pharmaceutical ingredient (API). After initially screening 15 structurally diverse APIs from 6 drug classes, appropriate mobile and stationary phases were selected and other operating parameters such as ABPR, gradient, temperature, and flow rate were optimized to obtain best retentivity, selectivity, and resolution. All enantiomeric drugs were efficiently resolved with a baseline resolution of ≥ 1.5 and elution run times of &lt;5 Mins. <br/>

Screening and rapid enantiomeric separation of different classes of chiral drugs by convergence chromatography

2019 Spring National Meeting

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