Pharmaceutical profiling method for lipophilicity and integrity using liquid chromatography-mass spectrometry

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, 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 Log D-7.4 (literature). The correlation of Log D-7.4 (literature) to Log D-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. (C) 2003 Elsevier Science B.V. All rights reserved.