CISPLATIN KINETICS

化学的实验与理论研究

Experimental and theoretical studies on the chemistry of cisplatin (DDP) have been continued with the goal of characterizing the reaction kinetics of the drug in vitro. Principal reactive species and pathways have been identified over the first 24 hours of drug reaction in various buffered inorganic solutions and plasma ultrafiltrates. Separation of drug aquation/hydrolysis products has been accomplished by reverse phase high-performance liquid chromatography with electrochemical detection. Parent, monoaquo and diaquo drug forms are detectable by this technique. Quantitative assessment has been enhanced by computing areas under chromatographic peaks rather than depending on peak heights, a significant improvement for monoaquo measurement since the peak of this compound appears on the shoulder of an oxygen peak. Experimental results have shown that DDP reacts with pure water at a rate close to that of its degradation in plasma ultrafiltrate, despite the high chloride content of the latter solution. While some of the plasma reactivity is attributable to small molecular weight nucleophiles such as methionine and perhaps bicarbonate, the