A Study of Miriplatin and Its Pt-metabolites in Beagle Dog Plasma by Size Exclusion Chromatography-Inductively Coupled Plasma Mass Spectrometry

A study of Pt-metabolites from a new anti-hepatoma drug miriplatin was important to miriplatin's pharmacology research. Therefore,a method based on size exclusion chromatography-inductively coupled plasma mass spectrometry( SEC-ICP-MS) was developed to study miriplatin and its Pt-metabolites in Beagle dog plasma. This method could be used to study total platinum concentration half-quantitatively. Compared with traditional ICP-MS direct determination,data acquired from this SEC-ICP-MS method were almost the same.By using BioSep-s2000 column,25 mmol /L of pH 7.2 phosphate buffer as eluent,and Pt-195 as detecting isotope,we discovered miriplatin with its four Pt-metabolites in dog plasma after intra-hepatic artery administration. The main Pt-metabolite was m2,which associated with plasma proteins. Miriplatin in plasma did not bind with plasma proteins. According to calculation,the ratio of miriplatin /m2 first decreased rapidly,and then slowly increased to its second climax,finally slowly decreased.