KINETIC-STUDIES OF THE REACTIVITY BETWEEN CISPLATIN AND ITS MONOAQUO SPECIES WITH L-METHIONIAE

Cisplatin readily undergoes reaction with L-met but little is known ab out the mechanism of their interactions. This paper deals with the stu dy of the reaction of L-met with various solutions of cisplatin: fresh aqueous [CP](1), saline [CP](2) and aquated [AP] which predominantly contained the monoaquo species. The initial rate of decrease of L-met concentration measured by HPLC-W after its incubation at 1:1 mole rati o with [CP](1), [CP](2) and [AP] was 0.1 mM h(-1) +/- 0.02, 0.24 mM h( -1) +/- 0.007 and 0.5 mM h(-1) +/- 0.04, respectively. Reactions of L- met with [CP](1), [CP](2) and [AP] after 24 h of incubation lead to th e formation of the same met-platinum adducts M1, M2, M3, M4 and M5 det ected by ICPMS. The structure of M2, M4 and M5 which were characterize d by LC-MS are in good agreement with those described by other investi gators using different methods while, M1 whose structure corresponded to cis-{Pt[(NH3)(2)(met)Cl]} was already postulated but never characte rized so far. The rate of hydrolysis of cisplatin into monoaquo specie s was evaluated to be 0.06 h(-1) +/- 0.006. In addition, the monoaquo species reacted more rapidly with L-met than cisplatin to yield M1. Th e latter species then underwent parallel reaction to give M2 which rea cted with L-met to give M5 via the formation of M3. This study shows t he higher reactivity with L-met of the monoaquo species relative to ci splatin and the usefulness of the combination of HPLC-UV-ICPMS and LC- MS for the characterization of platinum aminoacid adducts. (C) 1998 El sevier Science Inc. All rights reserved.