PARTITIONING PROPERTIES AND DEGRADATION KINETICS OF THE [NLE(4)-DPHE(7)]ALPHA-MSH ANALOG MELANOTAN-I (MT-T)

The objectives of this research were to determine the partitioning pro perties and the solution stability of the [Nle(4)-DPhe(7)]alpha-MSH an alog called Melanotan-I (MT-I). The apparent partition coefficients (A PC) were determined in two solvent systems, i.e. octanol-buffer and is ooctane-buffer in order to calculate Delta Log P.C. (partition coeffic ient) values. The Delta Log P.C. values at pH 2.5 and 7.4 were -0.307 and -0.409, respectively. The solution stability of MT-I was determine d by accelerated stability studies at 70 degrees, 80 degrees and 87 de grees C at pH 7.4 and ionic strength (mu) of 0.17. The energy of activ ation (E(a)) was Calculated to be 15.83 kcal/mol, resulting in an esti mated shelf life of 40 days at room temperature. From the pH-rate prof ile, MT-I was observed to be relatively stable under acidic conditions and exhibited greater degradation under basic conditions. Both ionic strength (mu = 0.15 to 1.5, at 0.05 M buffer concentration) and phosph ate buffer concentration (0.1-0.5 M, mu = 1.5) at pH 7.3 and 80 degree s C had no effect on the degradation kinetics of MT-I.