In an animal metabolism study, 14C-labeled compound X was orally dosed to lactating goats in dry feed. It was determined that once absorbed, Compound X was rapidly and extensively metabolized. In the milk and edible tissues analyzed by LCMSMS-TOF for the amine-label (liver, kidneys, muscle and fat), the primary Compound X related 14C metabolites were determined to be physiologically relevant moieties and result of bio transformational conversion of compound X to such molecules as diisopropylamine cysteine-glycine conjugate (liver), diisopropylamine cysteine conjugate (liver, kidney and muscle), and diisopropylamine glutathione conjugate (liver). However, three directly related small molecule metabolites were observed in the blood, GI tract content, urine and feces as a minor residue. The water extracts of liver, kidney and muscle contained high concentration of proteins and further characterization using SDS-PAGE indicated that 14C moiety derived from [Amine] or [Allyl] labels of Compound X was incorporated into natural constituents such as peptides and proteins, which were separated into radioactive protein bands on SDS-PAGE gel. The organic extracts of milk, and pooled fat contained lipid-type of radioactive residues, such as triglyceride derivatives, which were converted into fatty acid methyl ester after transesterification. This presentation will reveal challenges that our metabolism team had to overcome to determine the fate of Compound X in physiological environment, its conversion to directly related chemical-based metabolites and its biotransformation into physiologically relevant moieties.

Separation, isolation and identification of metabolic biotransformation products of a novel 14C-labeled small molecule (compound X) into proteins and peptides in a lactating goat and laying hen metabolism study

ACS Fall 2021

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