Determination and metabolism of dithiol chelating agents. III: Formation of oxidized metabolites of 2,3-dimercaptopropane-1-sulfonic acid in rabbit

Disulfide metabolites of 2,3-dimercaptopropane-1-sulfonic acid (DMPS), a heavy metal chelating agent, have been found in the urine of catheterized rabbits after a single dose of DMPS. After treating the urine with a reducing agent such as NaBH4, a 20-fold increase in DMPS was observed within 6 hr after administration. This suggested the presence of disulfide metabolites of DMPS. The disulfide metabolites were isolated from urine by extraction and were further purified by ion-interaction reverse phase HPLC. Upon reduction with NaBH4 or dithiothreitol, the isolated disulfides converted to DMPS. The isolated metabolites were not chelates of copper or zinc as determined by atomic absorption. Negative ion fast atom bombardment mass spectra indicated that the isolated metabolites were cyclic and acyclic polymeric disulfides of DMPS. The cyclic polymeric disulfides consisted of dimeric and trimeric forms of DMPS. One of the acyclic polymeric disulfides was identified as a DMPS dimer. Urinary excretion profiles of rabbits revealed that the majority of the altered DMPS consisted of cyclic and acyclic polymeric disulfides of DMPS. The cyclic disulfides increased with time while the acyclic disulfides decreased with time, suggesting that the acyclic forms are intermediates and oxidize to the cyclic forms. The rapid formation of stable 8-membered cyclic dimeric and 12-membered cyclic trimeric disulfides of DMPS strongly suggests that oxidation-reduction reactions are occurring. Both spontaneous and enzymatic oxidation mechanisms appear to be involved.