Bio Chem Press  Internet Electronic Journal of Molecular Design is a refereed journal for scientific papers regarding all applications of molecular design
Home | News | Current Issue | Journal Index | IECMD 2004 | Preprint Index | Instructions for Authors | Send the Manuscript | Special Issue
 BioChemPress.com  To bookmark this site press Ctrl D
 
   Home
   News & Announcements
  Journal Info
   Current Issue
   Journal Index
   Preprint Index
   Editor
   Advisory Board
  Conference Info
   IECMD 2004
   Day 1
   Day 2
   Day 3
   Day 4
   Day 5
   Day 6
   Day 7
   Day 8
   Day 9
   Day 10
   IECMD 2003
  BioChem Links
   CoEPrA
   Support Vector Machines
  Author Info
   Instructions for Authors
   Send the Manuscript
   Special Issue
  Contact
   Editorial Office
   Subscription
   Advertising
   Copyright
  User Info
   Terms of Use
   License

Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
ABSTRACT - Internet Electron. J. Mol. Des. April 2005, Volume 4, Number 4, 256-263

Chromatographic Estimation of Apparent Acid Dissociation Constants (pKa) in Physiological Resembling Conditions. A Case Study: Ionisable Non-Steroidal Anti-Inflammatory Drugs
Juan José Martínez-Pla, Laura Escuder-Gilabert, Salvador Sagrado, Rosa María Villanueva-Camañas, and María José Medina-Hernández
Internet Electron. J. Mol. Des. 2005, 4, 256-263

Free: Download the paper in PDF format Return to Table of Contents Get Acrobat Reader to view and print the paper

Abstract:
Biopartitioning micellar chromatography (BMC) is a mode of reversed phase micellar liquid chromatography that has proved to be useful in the description and prediction of several pharmacological properties of xenobiotics including oral drug absorption, ocular and skin drug permeability. The present paper deals with the application of BMC to modelling the acid dissociation constant (pKa values), consistent to physiological conditions, of eleven ionisable non-steroidal anti-inflammatory drugs (NSAIDs). The logarithm of the retention factor using 0.04 M Brij35 as mobile phase (logk4), of the set of compounds at two pH values, 5.5 and 7.4 and 36.5 °C, was measured. The difference between logk4 values at these pHs, dif_logk4 = logk4(pH=5.5) - logk4(pH=7.4), can be used to differentiate between ionisable (dif_logk4 > 0) and neutral (dif_logk4 = 0) NSAIDs. A quantitative retention-pKa relationship, can be used to estimate the pKa values of future ionisable NSAIDs. The BMC based model in the form pKa = b0 + b1 dif_logk4 (n = 11, r2 = 0.85, F = 52.7, SE = 0.26, q2 = 0.78) is made up of one descriptor. A leave-one-out test procedure shows that the predictive ability of the model for NSAIDs is good. The estimated values should be more reliable for drug discovery studies than the currently used estimated pKa (BMC) values in water at 25°C.

Free: Download the paper in PDF format Return to Table of Contents Get Acrobat Reader to view and print the paper

Home | News | Current Issue | Journal Index | IECMD 2004 | Preprint Index | Instructions for Authors | Send the Manuscript | Special Issue
Last changes: January 5, 2006 Webmaster
http://www.biochempress.com/
Copyright © 2001-2006 Ovidiu Ivanciuc