Hydrolysis of the tumor-inhibiting ruthenium[lll) complexes Hlm trans-[RnCl4(im)(2)] and Hlnd trans[RuCl4(ind)(2)] investigated by means of HPCE and HPLC-MS

High performance capillary electrophoresis (HPCE) as well as high performan ce liquid chromatography-mass spectrometry (HPLC-MS) have been applied to t he separation, identification and quantification of the tumor-inhibiting ru thenium compounds HIm trans-[RuCl4(im)(2)] (im=imidazole) and HInd trans-[R uCl4(ind)(2)] (ind=indazole) and their hydrolysis products. The half-lives for the hydrolytic decomposition of the Ru(III) compounds were determined b y monitoring the relative decrease of the original complex anion under diff erent conditions by means of capillary electrophoresis. The decomposition f ollows pseudo-first-order kinetics. The rate constants in water at 25 degre esC are 1.102+/-0.091x10(-5) s(-1) for HIm trans-[RuCl4(im)(2)] and 0.395+/ -0.014x10(-5) s(-1) for HInd trans-[RuCl4(ind)(2)]. About 8% of Him trans-[ RuCl4(im)(2)] but only about 2% of HInd trans-[RuCl4(ind)(2)] were hydrolyz ed after 1 h at room temperature. Whereas the hydrolysis rate of the imidaz ole complex is independent of the pH value, the indazole complex hydrolyzes much faster at higher pH. The half-life of HInd trans-[RuCl4(ind)(2)] in p hosphate buffer at pH 6.0 and 37 degreesC is 5.4 h, whereas it is less than 0.5 h at pH 7.4. In contrast to the imidazole complex, where no dependence on the buffer system was observed, hydrolysis of the indazole complex is e ven faster if a buffer containing hydrogen carbonate is used. The formation of [RuCl2(H2O)(2)(im)(2)](+) could be demonstrated by HPLC-MS measurements . In the case of the indazole complex, a release of the indazole ligands re sults in the formation of [RuCl4(H2O)(2)](-).