ABSTRACT
@#The conventional equilibrium dialysis and ultrafiltration methods cannot be used to determine the protein binding of some peptides because of their non-specific adsorption on the semipermeable membrane or poor stability in the plasma. The method of dextran-coated charcoal adsorption combined with LC-MS/MS were used. Based on the kinetic principle of initial rate of candidate drugs absorbed to dextran-coated charcoal, seven phosphorylated peptides with the same amino acid sequence and different configurations in rat plasma were selected as the study model using; the protein binding in rat plasma were determined; the amino acid distribution rules affecting the changes in protein binding rates of peptide candidate drugs were summarized. The results suggest that the dextran charcoal adsorption method, as a supplementary method for the determination of plasma protein binding, is suitable for peptides or organic drug candidates that cannot be determined by traditional techniques.
ABSTRACT
The research and development (R & D) of novel Chinese materia medica (CMM) have made a great progress in recent years.But problems still exist in druggability evaluation of novel CMM,such as uncertain evaluation content and lack of key technology.Druggability evaluation is the key to the success or failure for R & D of novel CMM.Observation on the effect and safety of novel CMM is the core of druggability evaluation.The important pharmacological problems include the choice of evaluation indicator,clinical indication,analysis of material basis,investigation of mechanism,research on pharmacokinetics and safety evaluation.Modem technologies should be used in druggability evaluation.We should have a correct understanding of the concept of novel CMM.The grasp of the meaning of novel drugs and the essence of CMM theory will be helpful for R & D of novel CMM.