A fast and reliable spectroscopic method for the determination of membrane-water partition coefficients of organic compounds

• Type: Article in International Scientific Journal
• Date: 2001

Authors

de Castro, B (Author) FCUP; Gameiro, P (Author) FCUP; Lima, JLFC (Author) FFUP; Matos, C (Author) Other; Reis, S (Author) FFUP

Journal

Title: Lipids

Vol. 36

Pages: 89-96

ISSN: 0024-4201

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 39 Citations

Scopus - 39 Citations

Scientific classification

FOS: Medical and Health sciences > Health sciences

Other information

Authenticus ID: P-000-XFP

DOI: 10.1007/s11745-001-0673-0

Abstract (EN): Partition coefficients (K-p) between Egg yolk phosphatidylcholine multilamellar vesicles and water were determined for two nonsteroidal anti-inflammatory drugs (indomethacin and acemetacin) using two independent methodologies: derivative spectrophotometry and variation of the experimental acidity constant in the presence of increasing vesicle concentration. Second-derivative spectrophotometry allowed for total elimination of background signal effects arising from lipid vesicles, without the need for separation techniques that may disturb equilibrium states. By using a model based on a simple partition, the values of K-p(T) can be obtained directly; furthermore, by performing determinations at two different pH values it is possible to calculate partition coefficients for the the neutral and negatively charged forms of the drugs (K-p(AH) and K-p(A)). In the other methodology, values of apparent acidity constants (K-app) were determined by spectrophotometry at different pH and different lipid concentrations, and an increase in K-app with decreasing lipid concentration was observed for both drugs, and from this dependence it was possible to calculate K-p(AH) and K-p(A-) for each drug. These values were used as a check those obtained by derivative spectroscopy, which has proven to be a reliable and more expeditious method to obtain K-p(AH) and K-p(A-).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8