title: Pharmaceutical profiling method for lipophilicity and integrity using liquid chromatography-mass spectrometry.
abstract: A method is described for the simultaneous profiling of sample lipophilicity, integrity, and purity. The method is rapid and is applicable to high throughput profiling of pharmaceutical properties in drug discovery. A short Polaris C(18) column is used with a rapid, wide-polarity mobile phase gradient, UV detection, and MS analysis. The lipophilicity of each component is estimated from a calibration curve using six drug or organic compounds and plotting their respective measured retention time versus LogD(7.4) (literature). The correlation of LogD(7.4) (literature) to LogD(7.4) (HPLC) for 60 structurally diverse drugs has a correlation coefficient r(2) of 0.89. The method is applicable to compounds with MW>200 and retention time>1.5 min for rapid, initial pharmaceutical profiling in drug discovery.
authors.affiliation: Wyeth Research, Chemical Sciences, Discovery Analytical Chemistry, CN8000, Princeton, NJ 08543-8000, USA. kernse@wyeth.com
authors.forename: Edward H
authors.initials: EH
authors.lastname: Kerns
authors.forename: Li
authors.initials: L
authors.lastname: Di
authors.forename: Susan
authors.initials: S
authors.lastname: Petusky
authors.forename: Teresa
authors.initials: T
authors.lastname: Kleintop
authors.forename: Donna
authors.initials: D
authors.lastname: Huryn
authors.forename: Oliver
authors.initials: O
authors.lastname: McConnell
authors.forename: Guy
authors.initials: G
authors.lastname: Carter
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D004364:Pharmaceutical Preparations