HPLC method for the determination of the purity of K[Pt(NH3)Cl3], a precursor of the platinum complexes with cytostatic activity

摘要

K[Pt(NH_3)Cl_3], 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(NH)3)_2Cl_2] or K_2[PtCl_4] 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(NH_3)Cl_3] 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. Intraassay precisions for the platinum complexes respective to their ions ([PtCl_4]~2_, [Pt(NH_3)Cl_3]_ and cis-[Pt(NH_3)_2Cl_2]) 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 [PtCl_4]~2_, [Pt(NH_3)Cl_3]_ and cis- [Pt(NH_3)_2Cl_2] were 6 μg. ml_~1, 13mg. ml_~1 and 5 μg. ml_~1 respectively, limits of quantification of [PtCl_4]~2_, [Pt(NH_3)Cl_3]_ and cis-[Pt(NH_3)_2Cl_2] were 51 μg. ml_~1, 55 mg. ml_~1 and 20 μg. ml_~1 respectively.