Holistic LC strategies, from UHPLC to HPLC and back

UHPLC has recently become a powerful tool in pharmaceutical analysis, specifically for method development, routine and rapid analysis. However, there are often limited numbers of UHPLC instruments available within internal and external customers and they do not always have access to this technology. This article gives an overview of the development and application of a holistic LC strategy to facilitate the implementation of UHPLC within a global Pharmaceutical Development function. An approach is being adopted that will enable the translation (geometric scaling) of chromatographic methods from “core” generic UHPLC methods with <2 μm columns to HPLC with ≥3 μm columns. There are requirements for UHPLC to HPLC transfer and practical issues to consider, specifically: instrument dwell volume differences, ensuring consistent selectivity across different particle sizes, frictional heating effects and pressure-induced retention effects. Finally the article demonstrates examples of UHPLC to HPLC translations and the application in AstraZeneca R&D projects.