Development and validation of a bioanalytical method based on LC–MS/MS analysis for the quantitation of CIGB-814 peptide in plasma from rheumatoid arthritis patients

Abstract:

CIGB-814, originally named as E18-3 APL1 or APL1 in preclinical experiments, is a novel therapeutic peptide candidate for Rheumatoid Arthritis (RA). It is an altered peptide ligand containing a novel CD4+ T-cell epitope of human heat shock protein 60 (83–109, MW 2988.38 g/mol) with a mutation (D100 → L) that increases its affinity for HLA-II type molecules associated to RA. A bioanalytical method, based on LC–MS/MS analysis, in the SRM mode was developed and fully validated to quantify this peptide in human plasma. An internal standard with the same amino acid sequence but labeled with three (13C615N2)-Lys residues was used for quantitation. The method provides a linear range from 1.5 to 48 ng/mL (without matrix effect and carry over) and an accuracy and precision good enough for monitoring more than 80% of the AUC of the PK profile in a phase I clinical trial. The peptide was administered …

Año de publicación:

2017

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Fuente:

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