Abstract
Solution stability of drug candidates in plasma, gastrointestinal fluids and bioassays is important in order to achieve low clearance, good oral bioavailability and have robust SAR. Screening of solution stability early in drug discovery can avoid pursuing hits with high risk of instability, prioritize chemical series, guide structural modification, and enhance the chance of project success. The conditions of solution stability methods are critical in generating relevant data and include: test compound concentration, enzyme source and preparation, limits of solubility, cosolvent, plasma protein binding effect, detection techniques (LC-UV vs. LC-MS), and what to detect (disappearance of parent vs. formation of degradants). Details of methodologies, applications, structure-stability relationships and case studies are discussed.
Keywords: Plasma stability, solution stability, simulated gastro-intestinal fluids, stability-ph profile, high throughput, drug discovery, HPLC, LC-MS
Current Drug Metabolism
Title: Solution Stability - Plasma, Gastrointestinal, Bioassay
Volume: 9 Issue: 9
Author(s): Li Di and Edward H. Kerns
Affiliation:
Keywords: Plasma stability, solution stability, simulated gastro-intestinal fluids, stability-ph profile, high throughput, drug discovery, HPLC, LC-MS
Abstract: Solution stability of drug candidates in plasma, gastrointestinal fluids and bioassays is important in order to achieve low clearance, good oral bioavailability and have robust SAR. Screening of solution stability early in drug discovery can avoid pursuing hits with high risk of instability, prioritize chemical series, guide structural modification, and enhance the chance of project success. The conditions of solution stability methods are critical in generating relevant data and include: test compound concentration, enzyme source and preparation, limits of solubility, cosolvent, plasma protein binding effect, detection techniques (LC-UV vs. LC-MS), and what to detect (disappearance of parent vs. formation of degradants). Details of methodologies, applications, structure-stability relationships and case studies are discussed.
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Cite this article as:
Di Li and Kerns H. Edward, Solution Stability - Plasma, Gastrointestinal, Bioassay, Current Drug Metabolism 2008; 9 (9) . https://dx.doi.org/10.2174/138920008786485218
DOI https://dx.doi.org/10.2174/138920008786485218 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
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