KINETICS OF THE FORMATION AND DECOMPOSITION OF 1,1'-ETHYLIDENEBIS[L-TRYPTOPHAN], AN EOSINOPHILIA MYALGIA SYNDROME-ASSOCIATED COMPOUND

1, 1'-Ethylidenebis[L-tryptophan] (EBT), an impurity found in L-trypto phan associated with eosinophilia myalgia syndrome (EMS), has been sug gested as one of the causative agents for EMS. Highperformance liquid chromatography was used to study the kinetics of EBT formation and dec omposition in buffer systems. Initial EBT decomposition was first-orde r with respect to EBT and strongly pH-dependent. The pH profile sugges ted that decomposition involved the addition of one proton. The value of the critical pH, above which the rate of EBT decomposition remained constant, was determined to be 4.8. The rate of EBT decomposition inc reased with increasing temperature, and the activation energy was calc ulated to be 12.5 kcal/mol. The rate of EBT formation decreased with i ncreasing pH and decreasing temperature. The presence of excess acetal dehyde increased EBT formation to a lesser extent than did the presenc e of excess L-tryptophan. The results of this study are consistent wit h the hypothesis that EBT was formed during the absorption stage of th e cation exchange operation in the commercial process that resulted in the formation of EMS-associated L-tryptophan.