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

Author(s): William L. Fitch*, Cyrus Khojasteh, Ignacio Aliagas, Kevin Johnson

Journal Name: Drug Metabolism Letters

Volume 12 , Issue 2 , 2018

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Graphical Abstract:


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.

Methods: 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.

Keywords: Drug metabolite identification, liquid chromatography, mass spectrometry (MS), RT prediction, RT, CHI system.

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Article Details

Year: 2018
Published on: 22 November, 2018
Page: [93 - 100]
Pages: 8
DOI: 10.2174/1872312812666180802093347

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