A 21st Century HPLC Workflow for Process R&D

Abstract

A unique high-performance liquid chromatographic (HPLC) workflow specifically designed for the rigors of process development has been developed. A key feature of the workflow is the creation of an HPLC software–hardware platform designed to automatically and systematically screen samples using a matrix of columns and eluents to aggressively search for impurities. The workflow platform was assembled from commercial hardware components and both custom and commercial HPLC software. The platform can be used to challenge existing HPLC methods or to develop new methods. The screening conditions are complementary to each other, and are useful to assess the complexity of a sample and to chromatographically resolve impurities that may coelute using any single method. The workflow has been designed to support several different modes of HPLC, and can be used with absorption detection, photodiode array spectrometers, evaporative light scattering (ELS) devices, and mass spectrometric (MS) detection. The custom software interface contains a data-viewing feature to simplify analysis of results. The platform is designed to be used by process scientists, and the same simple user-interface is used to control analytical HPLC, LC–MS, and preparative HPLC. Three real world examples are provided to illustrate the utility of the platform to rigorously assess the complexity of samples and to develop new and improved HPLC methods. (JALA 2005;10:381–93)