Lipophilicity is an important physicochemical property which influences pharmacokinetic, pharmacodynamics and toxicological behaviour of drugs. Although the LogD octanol:water shake flask is a common method to assess lipophilicity, alternative approaches such as the chromatographic hydrophobicity index (CHI) are now being used in many large scale screening projects to reduce interference from impurities, decrease compound requirements and save time and cost.
For a given HPLC reverse phase set-up, a CHI value is determined by normalising the retention time of a compound using a linear curve based on a set of calibration compounds with known CHI values. The resultant CHI value can be further converted to a CHI LogD value using an established linear regression equation. Typically, HPLC with UV detection has been used to determine CHI, however, this detection method presents significant throughput limitations. In a recent poster presented at the HT-ADME 2021 event, Cyprotex demonstrate the use of time of flight mass spectrometry as a detection method for CHI. This approach has several advantages compared to UV detection including the ability to analyse mixtures of compounds in cassette sizes of up to 30, and improved sensitivity and selectivity.
The poster presents the full analytical method and demonstrates the reproducibility and robustness of the technique including its comparison against literature values.
Learn more about the benefits of using CHI as a rapid ultra-high throughput method for lipophilicity determination.