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 C18 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 D7.4 (literature). The correlation of Log D7.4 (literature) to Log D7.4 (HPLC) for 60 structurally diverse drugs has a correlation coefficient r2 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.