Determination of plasma protein binding of peptide drug candidates by dextran-coated charcoal
- VernacularTitle:葡聚糖木炭吸附法测定多肽类候选药物的血浆蛋白结合率
- Author:
Li ZHANG
1
;
Cheng JIANG
;
Simin CHEN
;
Ting YAO
;
Ningling Xiang
;
Mengxiang SU
;
Bin DI
Author Information
1. 中国药科大学药学院
- Collective Name:10.11665/j.issn.1000-5048.20200503
- Publication Type:Journal Article
- Keywords:
peptides;
plasma protein binding;
dextran-coated charcoal adsorption;
druggability evaluation;
LC-MS/MS
- From:
Journal of China Pharmaceutical University
2020;51(5):522-529
- CountryChina
- Language:Chinese
-
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.
