Wittrisch H, Schröer H P, Vogt J, Vogt C
Institute of Analytical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Germany.
Electrophoresis. 1998 Nov;19(16-17):3012-7. doi: 10.1002/elps.1150191636.
Titanocene dichloride is one of the most promising cancerostatica of the future: nevertheless, its high activity against several tumor cells was discovered 20 years ago. Detailed knowledge of the mechanism of hydrolysis of titanocene dichloride and its stability in the infusion liquid is a prerequisite for clinical tests and for a successful application for permission as medication. Capillary electrophoresis (CE) was used to observe the hydrolysis behavior of titanocene dichloride in aqueous solutions. The hydrolysis products were separated in a 20 mM phosphate buffer, pH 6, and in a 20 mM malic acid buffer, pH 3. Up to five hydrolysis products were obtained. A significant 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 (PIXE) detection technique. The results obtained correspond with the hydrolysis mechanism described in the literature. The determination of free titanocene dichloride in human plasma failed due to the high affinity of the plasma proteins for this compound.
然而，20年前就已发现它对多种肿瘤细胞具有高活性。详细了解二氯二茂钛的水解机制及其在输液中的稳定性是进行临床试验以及成功申请药物许可的前提条件。采用毛细管电泳（CE）观察二氯二茂钛在水溶液中的水解行为。水解产物在pH 6的20 mM磷酸盐缓冲液和pH 3的20 mM苹果酸缓冲液中进行分离。最多可得到五种水解产物。观察到样品制备（pH、等离子添加剂）对水解速率有显著影响。通过紫外扫描和元素选择性粒子诱导X射线发射（PIXE）检测技术对水解产物进行了表征。所得结果与文献中描述的水解机制相符。由于血浆蛋白对该化合物具有高亲和力，因此未能测定人血浆中的游离二氯二茂钛。
