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Updated: Feb 6, 2026

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
Published on: September 25, 2017
Interpretation of in Vitro Metabolic Stability Studies for Racemic Mixtures
James A Baker1, Michael D Altman1, Iain J Martin1
1Pharmacokinetics, Pharmacodynamics & Drug Metabolism and Modeling & Informatics, MRL, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Abstract:
In early drug discovery, where chiral syntheses may not yet have been elucidated or enantiomeric separation is not feasible, screening of racemates in metabolic stability assays may offer a pragmatic approach. To assess the risk of incorrectly deprioritizing enantiomers due to misclassification of apparent in vitro intrinsic clearance (CLintapp), we evaluated (1) theoretical simulations; (2) literature on enantiomeric CLintapp differences; (3) historic MSD data; and (4) new data on enantiomers with high eudysmic ratios and low predicted three-dimensional similarity. Overall, the results suggested minimal risk of not progressing an enantiomer due to an appreciably different (>3-fold) racemate CLintapp.
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