Using LC Retention Times in Organic Structure Determination: Drug Metabolite Identification.

BACKGROUND: There is a continued need for improvements in the efficiency of metabolite structure elucidation.

OBJECTIVE: We propose to take LC retention time (RT) into consideration during the process of structure determination.

METHOD: Herein we develop a simple methodology that employs a chromatographic hydrophobicity index (CHI) framework for standardizing LC conditions and introduce and utilize the concept of a predictable CHI change upon Phase 1 biotransformation (CHIbt). Through the analysis of literature examples, we offer a quantitative structure retention relationship (QSRR) for several types of biotransformation (especially hydroxylation) using physicochemical properties (clogP, hydrogen bonding).

RESULTS: The CHI system for retention indexing is shown to be practical and simple to implement. A database of CHIbt values has been created from re-incubation of 3 compounds and from analysis of an additional 17 datasets from the literature. Application of this database is illustrated.

CONCLUSION: In our experience, this simple methodology allows complementing the discovery efforts that saves resources for in-depth characterization using NMR.