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A Simple Procedure for Determining the Aqueous Half-Lives of Pyrrolic Metabolites of Pyrrolizidine Alkaloids

R A Cooper, R J Huxtable

Toxicon. 1996 May;34(5):604-7.

PMID: 8783455

Abstract:

We report a simple and rapid procedure for estimating the aqueous half-lives of the reactive metabolites of pyrrolizidine alkaloids that are responsible for toxicity. The metabolites (dehydroalkaloids; DHAs) were rapidly added to a 0.5 mM HEPES solution, pH 8.0. The subsequent fall in pH, due to ester hydrolysis, was followed potentiometrically. The change in pH was well described by single-component exponential decay, allowing the derivation of rate constants and half-lives of hydrolysis. Half-lives varied from 0.31 sec for dehydro-7-acetyllycopsamine to 5.36 sec for dehydrotrichodesmine. The results support the view that alkaloids whose DHA metabolites have longer half-lives produce greater extrahepatic toxicity.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP73544486 7-Acetyllycopsamine 7-Acetyllycopsamine 73544-48-6 Price
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