Structure-interaction relationships between the bile acid GCA and pharmaceuticals using multivariate data analysis and capillary electrophoresis
2007 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 96, no 8, 2057-2073 p.Article in journal (Refereed) Published
Capillary electrophoresis (CE) has been used in an interaction study of 66 pharmaceutical compounds with the bile acid glycocholate (GCA). The developed method proved to have a high precision in its ability to determine the mobility of drugs in buffer and buffer bile acids solutions. The relationship between solute structure and interaction with GCA was studied using two-dimensional descriptors with the in-house software SELMA and a three-dimensional model (quantum mechanical descriptors) in combination with the experimental CE-interaction data. The multivariate analysis method used was projection to latent structures by means of partial least squares (PLS). Two selections of training and test set were used for evaluation of a two-class model on interaction data. In the first selection all observations were used for training set, for example, creating a model, and re-predicting the observations on the model. A successful prediction on 85% of the drugs was observed using this model. The second selection used the 21 first tested compounds in the training set, where 78% of the compounds were correctly predicted using the two-dimensional model (SELMA) on the remaining 45 compounds and, respectively, 82% using the three-dimensional (quantum mechanical) model. Analysis of the impact of the descriptors showed that descriptors relating to hydrophobicity have a large positive effect on the interaction. Descriptors relating to polar properties have a pronounced negative effect on the interaction of drugs with bile acids.
Place, publisher, year, edition, pages
2007. Vol. 96, no 8, 2057-2073 p.
analytical chemistry, structure-property relationship (SPR), multivariate analysis, electrophoresis, bile acid transporters
IdentifiersURN: urn:nbn:se:uu:diva-11423DOI: 10.1002/jps.20852ISI: 000248427900017PubMedID: 17286289OAI: oai:DiVA.org:uu-11423DiVA: diva2:39192