1H NMR study of monocrotaline and its metabolites in human blood

► Both human plasma and red blood cells (RBCs) can transport monocrotaline (MCT) and its metabolites. ► MCT (46%) and its toxic metabolite dehydromonocrotaline (DHM, 49%) were taken into RBCs in 30min. ► In plasma MCT remained intact and weakly associated with plasma proteins. ► DHM was rapidly hydrolyzed to a reactive pyrrolic metabolite in plasma. Monocrotaline (MCT) is a naturally occurring hepatotoxic pyrrolizidine alkaloid found in plants. This investigation is aimed at furthering the understanding of the role of blood in mediating the transport of MCT and its reactive metabolites in humans. Reactions of monocrotaline and its metabolites, dehydromonocrotaline (DHM), retronecine (RET) and dehydroretronecine (DHR) with human blood plasma, red blood cells (RBCs), and whole blood were studied in vitro by proton nuclear magnetic resonance spectroscopy. In plasma MCT remained intact and weakly associated with plasma proteins, and DHM was rapidly hydrolyzed releasing necic and lactone acids, and the reactive pyrrolic metabolite. MCT and its metabolite DHM were internalized in RBCs to the extent of 46.0% and 48.9% respectively in 30min. No polymerization of DHR was observed when incubated with plasma and RBCs. The data clearly showed that both human plasma and RBCs could be the carriers for the transportation of MCT and its metabolites, DHM, RET and DHR between organs and could stabilise the reactive MCT metabolite DHR.