AN AUTOMATED MULTIDIMENSIONAL SCREENING APPROACH FOR RAPID METHOD DEVELOPMENT IN HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

Despite enormous advancements in the area of high performance liquid c hromatography (HPLC) in recent years, method development remains a maj or challenge. This is primarily due to the unknown nature of the matri x material which sometimes is difficult to characterize (e.g. biologic al matrices). To improve the efficiency of method development a multid imensional screening approach was presented. This approach was based o n two major steps: (1) a matrix spiked with drug was eluted from a lar ge number of columns, each under different mobile phase compositions, to provide the preliminary selectivity-separation information; (2) thi s information was then used to compose column switching pairs (each pa ir consisted of a preparatory column followed by an analytical column) and the elution profile was evaluated to determine the suitable clean up and quantitation conditions. An example was provided using ethyl 3 ,5-bis(acetylamino)-2,4,6-triiodobenzoate (EEDA), an X-ray enhancement agent, in human plasma. Since the HPLC system was fully automated the data generation time, and consequently the method development time, c an be significantly reduced. (C) 1997 Elsevier Science B.V.