HPLC Method for the Determination of the Purity of K[Pt(NH3)Cl3], a Precursor of the Platinum Complexes with Cytostatic Activity

Abstract

K[Pt(NH3)Cl3], a valuable precursor for the preparation of platinum complexes with cytostatic activity, e.g. satraplatin, picoplatin, LA-12 and cycloplatam, is currently prepared from cis-[Pt(NH3)2Cl2] or K2[PtCl4] and these are the usual impurities in the final product. A simple, selective and sensitive HPLC-UV analytical method for the determination of the purity of K[Pt(NH3)Cl3] and the quantification of the impurities has been developed and validated. The platinum complexes present in the final product were separated on a strong base ion exchange column by the gradient elution with detection at 213 nm. Intra-assay precisions for the platinum complexes respective to their ions ([PtCl4]2−, [Pt(NH3)Cl3]− and cis-[Pt(NH3)2Cl2]) were between 0.1 and 2.0% (relative standard deviation); intermediate precisions were between 1.4 and 2.0% and accuracies were between 98.6 and 101.4%. Limits of detection of [PtCl4]2−, [Pt(NH3)Cl3]− and cis-[Pt(NH3)2Cl2] were 6 µg · ml−1, 13 mg · ml−1 and 5 µg · ml−1 respectively, limits of quantification of [PtCl4]2−, [Pt(NH3)Cl3]− and cis-[Pt(NH3)2Cl2] were 51 µg · ml−1, 55 mg · ml−1 and 20 µg · ml−1 respectively.