ISSN:
1573-904X
Keywords:
muramyldipeptide
;
hydrolysis kinetics
;
parenteral formulation
;
high-pressure liquid chromatography (HPLC)
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The degradation of muramyldipeptides (MDPs) in aqueous solution obeys the rate law k obs = k H+αH+ + k o + k HO- a HO- and the Arrhenius equation. For example, the rate constants for degradation of N-acetylmuramyl-L-threonyl-D-isoglutamine, 3, at 25°C are k H+ = 2.3 × 10−6 M −1 sec−1, k o = 8.2× 10−10 sec−1, and k HO− = 0.19 M −l sec−1. The degradation rates are dependent on the side-chain substituents; it is predicted that sterically hindered MDP compounds will show an extended shelf life in aqueous solution. Product studies in the weakly acid pH region (where the pH of maximum stability occurs) show that MDP compounds degrade largely by hydrolysis of the dipeptide side chain. These data show that MDP 3 exhibits a shelf life (t 90) of greater than 2 years in aqueous solutions of pH 4–4.5, the pH of maximum stability.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1015929610687
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