Automated Column Screening and Computer-Assisted Modeling for Analysis of Complex Drug Samples in Pharmaceutical Laboratories

New drug substances pose challenging process chemistry which requires adequate and fast advancement in analytical tools to avoid bottlenecks in drug development. Challenges encountered in analyzing new medicines are beyond the complexities encountered during the manufacturing process, especially for biopharmaceuticals and multi-combination drugs. Fast and reliable analytical assays are needed to determine composition, presence of process impurities and intermediates, heterogeneities in structure, aggregation and degradation products, etc. The development of such methods is enabled by the availability of modern instrumentation, predictive tools, novel stationary phases, characterization techniques, etc. In this work, we highlight some of the novel analytical technologies and tools used in pharmaceutical R&D laboratories for streamlining method development and generation of accurate data to enable multiple pipeline programs. A crucial step in method development includes systematic exploration of chromatography columns and mobile phases to find the right combination of column and mobile phase needed to achieve the targeted resolution between analytes. The best chromatographic method obtained from screening can be further optimized by chromatographic-modeling software based on a minimum number of experiments. Herein, the need for automated screening systems and computer-assisted modeling is highlighted through examples of methods developed for small and large molecule drugs, while highlighting challenges encountered specifically with analytical method development for large-molecule drugs.