Determination of titanocene, a new drug with anticancer potential, and itsmetabolism in solution by capillary electrophoresis

Titanocene dichloride is one of the most promising cancerostatica of the fu ture: nevertheless, its high activity against several tumor cells was disco vered 20 years ago. Detailed knowledge of the mechanism of hydrolysis of ti tanocene dichloride and its stability in the infusion liquid is a prerequis ite for clinical tests and for a successful application for permission as m edication. Capillary electrophoresis (CE) was used to observe the hydrolysi s behavior of titanocene dichloride in aqueous solutions. The hydrolysis pr oducts were separated in a 20 mM phosphate buffer, pH 6, and in a 20 mM mal ic acid buffer, pH 3. Up to five hydrolysis products were obtained. A signi ficant influence of the sample preparation (pH, isoionic additives) on the hydrolysis rate was observed. The hydrolysis products were characterized by the UV scan and the element-selective particle-induced X-ray emission (PIX E) detection technique. The results obtained correspond with the hydrolysis mechanism described in the literature. The determination of free titanocen e dichloride in human plasma failed due to the high affinity of the plasma proteins for this compound.