title: An automated multidimensional screening approach for rapid method development in high performance liquid chromatography.
abstract: Despite enormous advancements in the area of high performance liquid chromatography (HPLC) in recent years, method development remains a major challenge. This is primarily due to the unknown nature of the matrix material which sometimes is difficult to characterize (e.g. biological matrices). To improve the efficiency of method development a multidimensional screening approach was presented. This approach was based on two major steps: (1) a matrix spiked with drug was eluted from a large number of columns, each under different mobile phase compositions, to provide the preliminary selectivity-separation information; (2) this information was then used to compose column switching pairs (each pair 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, can be significantly reduced.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Nycomed R&D, Wayne, PA 19087, USA.
authors.forename: D
authors.initials: D
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Berna
authors.forename: G
authors.initials: G
authors.lastname: Maier
authors.forename: J
authors.initials: J
authors.lastname: Johnson
mesh_terms: D000097:Acetonitriles; D001565:Benzoates / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D005663:Furans; D006801:Humans; D007451:Iodamide / Q000032:analysis; D011838:Radiation-Sensitizing Agents / Q000032:analysis; D015203:Reproducibility of Results
chemical_list: D000097:Acetonitriles; D001565:Benzoates; D005663:Furans; D011838:Radiation-Sensitizing Agents; C111724:ethyl 3,5-bis(acetylamino)-2,4,6-triidobenzoate; C018674:tetrahydrofuran; D007451:Iodamide; C032159:acetonitrile