title: High-speed solubility screening assay using ultra-performance liquid chromatography/mass spectrometry in drug discovery.
abstract: Ultra-performance liquid chromatography (UPLC) was investigated as an alternative to high-performance liquid chromatography (HPLC) for analyzing pharmaceutical drug candidates. We previously developed a 96-well-based high-speed solubility assay system (HSSOL) using HPLC/UV and a LogD assay system (HSLogD) using HPLC/MS [Y. Dohta, T. Yamashita, S. Horiike, T. Nakamura, T. Fukami, Anal. Chem. 79 (2007) 8312]. We have introduced the UPLC/MS system into this previously developed HSSOL system to increase throughput. Results obtained by the UPLC/MS and HPLC/UV systems showed good agreement, validating the usefulness of the UPLC/MS system. A high-speed solubility assay system was developed employing the UPLC/MS system, thereby tripling the throughput.
authors.affiliation: Tsukuba Research Institute, BANYU Pharmaceutical Co. Ltd., 3 Okubo, Tsukuba, Ibaraki 300-2611, Japan. taro_yamashita@merck.com
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yukifumi
authors.initials: Y
authors.lastname: Dohta
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods*; D015394:Molecular Structure; D015203:Reproducibility of Results; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*