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Determination of drug–plasma protein binding using human serum albumin chromatographic column and multiple linear regression model
Author(s) -
Beaudry Francis,
Coutu Michel,
Brown Nigel K.
Publication year - 1999
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/(sici)1099-0801(199910)13:6<401::aid-bmc899>3.0.co;2-c
Subject(s) - chemistry , chromatography , human serum albumin , plasma protein binding , serum albumin , albumin , linear regression , blood proteins , pharmacokinetics , biochemistry , pharmacology , medicine , machine learning , computer science
Reversible attachment to serum proteins plays a significant role in pharmacokinetics and pharmacodynamics, and a clear understanding of this process is fundamental in the development of the rational use of many therapeutics agents. Over the last few years, it has been demonstrated that immobilized human serum albumin (HSA) could be used to estimate plasma protein binding. A series of 40 structurally unrelated pharmaceutical compounds were chromatographed on an immobilized HSA column in order to construct a protein binding ‘calibration curve’ and multiple linear regression system. When studying the relationship between the chromatographic retention and the percentage of binding determined in vitro , a good correlation can be observed ( r 2 = 0.799) using a wide variety of compounds with different binding affinities (from 0 to 99% binding). Using a quantitative structure–retention relationships (QSRR) approach to analysing chromatographic data, the correlation was improved compared to the traditional approach ( r 2 = 0.824). Copyright © 1999 John Wiley & Sons, Ltd.