Demonstrative validation study employing a packed column pressurized fluidchromatography method that provides assay, achiral impurities, chiral impurity, and IR identity testing for a drug substance

Assay development, assay validation, and documentation are reported here fo r a single packed column pressurized fluid chromatographic/ultraviolet (UV) method that provides: (1) simultaneous detection and quantification for th e chiral drug, the chiral impurity and seven achiral impurities; and (2) a Fourier transform infrared (FT-IR) spectrometric identification test result for the Searle drug substance sample, xemilofiban. The separation is achie ved in less than 30 min with three columns in tandem and a gradient of CO2- CH3OH. The post-column flow is split between UV (assay) and FT-IR (identifi cation). Precision and accuracy are consistent within figures of merit obta ined by liquid chromatographic-ultraviolet assays on analogous drug substan ces. The reported procedure combines three typical drug substance tests int o one test (e.g. chiral impurities, achiral impurities, and infrared identi fication). (C) 2001 Elsevier Science B.V. All rights reserved.