Rapid Development of a Bromochloropyridine Regioisomer Purity Method Enabled by Strategic LC Screening

Abstract With the intent to provide aligned, impactful, and efficient strategies for liquid chromatography method development, tier-based stationary/mobile phase screening workflows have been implemented in the Chemical Process Development department at Bristol Myers Squibb. These workflows are utilized as tools that enable more rapid method generation for early to mid-stage clinical development programs. An illustrative example of applying this approach was the method development for 3-bromo-2-chloropyridine and six of its positional isomeric impurities. Several parameters (gradient time, flow rate, column geometry, particle size, temperature, and solvent effects) were evaluated to achieve a baseline resolved separation for this challenging mixture. The impact that the screening workflows have regarding timesavings, effort, and resourcing to develop and optimize this LC method will be discussed.