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.

Keywords:

• cis-diamminedichloroplatinate(II)
• HPLC-UV
• Ion exchange liquid chromatography
• Latinum complexes
• Potassium amminetrichloroplatinate(II)
• Potassium tetrachloroplatinate(II)

Acknowledgments

We gratefully acknowledge the Ministry of Industry and Trade of the Czech Republic project 2A-2TP1/049 and Grant Agency of the Czech Republic project 203/08/H032-1 for supporting this research financially.

Notes

^(a) vs. K[Pt(NH₃)Cl₃].

Acceptance criteria R ²  > 0.998. ^(a)x [µg.ml⁻¹].

Acceptance criteria ≤2% for assay ≤2% for assay 98–102% for assay.