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  • Title: [The kinetics of neostigmine degradation in aqueous solution].
    Author: Porst H, Kny L.
    Journal: Pharmazie; 1985 Oct; 40(10):713-7. PubMed ID: 4080787.
    Abstract:
    The concentration course of the degradation products of aqueous temperature-stressed solutions of neostigmine bromide (1) shows, that 1 simultaneously is hydrolyzed to 3-hydroxyphenyltrimethylammonium bromide (2) and demethylated to 3-dimethylaminophenyldimethylcarbamate (4). The ester hydrolysis is the rate-determining predominant reaction and of pseudo first-order. Under temperature-stressed conditions only, the demethylation to 4 followed by consecutive reactions proceeds at a measurable rate. The kinetic parameters of the ester hydrolysis calculated from the results of isothermic short-term tests permit the prediction of a five-year stability of 2% neostigmine solutions in the therapeutically relevant pH-value range from 3 to 7. On the basis of the kinetic results the possible reaction mechanisms and the influence of selected components on the rate of the hydrolysis and demethylation are discussed.
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