Peptide drugs stability determination

Determination of aluminium in water for injection as a fluorescent complex Determination of stability of peptide drugs in solution Fluorescent derivatives and flow injection analysis... 

Synthetic peptides often lack the conformational stability required for a successful drug therefore determination of peptide stability in serum constitutes a powerful and important screening assay for the elimination of unstable peptides in the pipeline of drug development (see Note 1). Peptide stability in serum can rather easily be determined by reverse phase-high-performance liquid chromatography (RP-HPLC) and mass spectroscopy (MS) from both in vitro and in vivo studies. 

BSA was used as model protein drug to determine the release behavior of protein or peptide from protein loaded composite hydrogel in vitro. The detail procedure was similar to the study of VB12 release, but the initial drug loading amount were 4mg. The amount of BSA present in the supernatant was determined by bicinchoninic acid (BCA) assay and BCA Protein Assay Kit (PIERCE, USA) was used. The SDS-polyacrylamide gel electrophoretic (PAGE) analysis was used to assay the stability of BSA during the release period. 

Stability prediction for peptide and protein drugs under accelerated testing conditions is possible if the temperature dependence of the degradation rate is determined and found to be well behaved. The temperature dependence can often be represented by the Arrhenius equation, as was seen with small-molecule drugs. Linear Arrhenius plots and the values of apparent activation energy calculated from the slopes have been reported for chemical degradation of various peptides in aqueous solutions. Values of approximately 20 kcal/mol... 

Biological and clinical studies have underlined the fundamental importance of the polymer-drug linker. When a conjugate is administered parenterally its stability in the circulation and ability to release drug at an appropriate rate on arrival in the target tissue is a principal determinant of therapeutic index. A variety of chemistries can be used to create pendant linkers (Fig. 5) (10). Lysosomally degradable peptides ensure site-specific intracellular activation, but many drug candidates do not have a convenient aliphatic -NH2 for this purpose. 

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