Highly sensitive LC‐MS method for stereochemical quality control of a pharmaceutical drug substance intermediate

Abstract

Stereochemical quality control for pharmaceutical drug substance intermediates is a daunting task, especially considering the need to separate multiple stereoisomers simultaneously with low ppm level sensitivity. To address these challenges, we have successfully implemented chiral column screening, and developed an ultrasensitive liquid chromatography–mass spectrometry (LC‐MS) method to separate four stereoisomers including the API intermediate, its enantiomer, and two other diastereomers. Parameters such as mobile phase additives, MS fragmentor, and column temperature were optimized to achieve the desired selectivity and sensitivity. The method enabled stereoisomer detection with high sensitivity (2 ppm LOD and 5 ppm LOQ), good linearity, and desired spike recovery, and it has been successfully applied for stereoisomer quantitation in multiple large‐scale batches and demonstrated chiral quality control of the drug substance intermediate.

Information technology system to promote drug production command supervision

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