Abstract

E-2078 is a dynorphin A (1–8) analog, [N-methyl-Tyr¹, N-methyl-Arg⁷-d-Leu⁸] Dyn A (1–8) ethylamide. Its biochemical stability against enzymatic degradationin vitro in human and rhesus monkey blood, and in vivo in rhesus monkey blood was studied using matrix-assisted laser desorption/ionization mass spectrometry. In vitrostudies were carried out in freshly drawn human and rhesus monkey blood, incubated at 37°C for various time periods. In vivostudies were conducted by E-2078 i.v. injection to rhesus monkeys, and blood samples were collected at various time points after the injection. It was found that E-2078 was stable against enzymatic degradation in vitro in freshly drawn human and rhesus monkey blood. Minor biotransformation products from E-2078, such as E (1–4), E (1–5) and E (3–6), were detected in vitro in some human and rhesus monkey blood, but they made up less than 5% of the total starting E-2078 peptide. No biotransformation products were detected in the blood samples from in vivo studies. The apparent half-life of elimination of E-2078 in vivo from the rhesus monkey blood was determined to be 44.0 min.