Development of predictive retention-activity relationship models of antipsychotic drugs by micellar liquid chromatography.
The predictive and interpretative capability of quantitative chromatographic retention-biological activity models is supported by the fact that in adequate experimental conditions the solute partitioning into the chromatographic system can emulate the solute partitioning into lipid bilayers of biological membranes, which is the basis of drug and metabolite uptake, passive transport across membranes and bioaocumulation. The use of micellar solutions of Brij35 as mobile phases in reversed liquid chromatography has proven to be valid in predicting some biological activities of different kinds of drugs. In this paper, the correlations between the logarithm of capacity factors and pharmacokinetic, preclinical pharmacology and therapeutic efficacy parameters of phenothiazines are studied. Parabolic quantitative retention-activity relationship models with predictive and interpretative ability have been obtained.
Martín-Biosca
Y
Y
Departamento de Química Analítica, Universidad de Valencia, C/Vicente Andrés Estellés s/n, E-46100 Burjassot, Valencia, Spain.
Molero-Monfort
M
M
Sagrado
S
S
Villanueva-Camañas
R M
RM
Medina-Hernández
M J
MJ
D000818:Animals; D014150:Antipsychotic Agents / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D020128:Inhibitory Concentration 50; D010640:Phenothiazines / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D015203:Reproducibility of Results; D013997:Time Factors
D014150:Antipsychotic Agents; D010640:Phenothiazines