Kinetics of decomposition of chemically unstable metabolites in the presence of nucleophiles: derivation of equations used in graphical analyses.

The present paper provides a theoretical base for the development of various plots that may be used in studying the sequence of events that occur when the reaction of a chemically reactive intermediate with an exogenous nucleophile is pseudo first order, and all of the other reactions by which the initial reactive metabolite decomposes are either first order or pseudo first order. Several hypothetical models that should represent most of the decomposition mechanism of chemically reactive intermediates are discussed. Problems in assessing the kinetic characteristics of diffusional barriers of the intermediates and of enzymatic reactions in the inactivation of chemically reactive intermediates are raised and the possible solution of such problems are pointed out.