DYNORPHIN-A (1-8) ANALOG, E-2078, IS STABLE IN HUMAN AND RHESUS-MONKEY BLOOD

E-2078 is a dynorphin A (1-8) analog, [N-methyl-Tyr(1), N-methyl-Arg(7 )-D-Leu(8)] Dyn A (1-8) ethylamide. Its biochemical stability against enzymatic degradation in vitro in human and rhesus monkey blood, and i n vivo in rhesus monkey blood was studied using matrix-assisted laser desorption/ionization mass spectrometry, In vitro studies were carried out in freshly drawn human and rhesus monkey blood, incubated at 37 d egrees C for various time periods. In vivo studies were conducted by E -2078 i.v. injection to rhesus monkeys, and blood samples were collect ed at various time points after the injection. It was found that E-207 8 was stable against enzymatic degradation in vitro in freshly drawn h uman 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 t he total starting E-2078 peptide. No biotransformation products were d etected in the blood samples from in vivo studies. The apparent half-l ife of elimination of E-2078 in vivo from the rhesus monkey blood was determined to be 44.0 min.