Investigation on the Decomposition of Carboplatin in Infusion Solutions

Abstract

A high performance liquid chromatographic (HPLC) method to study the stability of carboplatin (cis-diammine(1,1-cyclobutanedicarboxylato)-platinum(II)) in commercial products was developed and validated according to the recommendations of the International Harmonization Conference [1]. For analytical applications a Nucleosil-100-5 C18 column and an isocratic system of CH3OH/(0.001 N H2SO4/0.02 M Na2SO4) 5/95 (V/V) or 10/90 (V/V) at a flow rate of 0.6 ml/min with UV spectroscopic detection at λ = 220 nm was used. It allows a quantification of carboplatin and 1,1-cyclobutanedicarboxylic acid (CBDCA) with limits of 1.03 × 10−4 mg/ml ( = 2.8 × 10−4 mol/l carboplatin) and 2.8 × 10−3 mg/ml ( = 1.9 × 10−2 mol/l CBDCA), respectively. Investigations on a carboplatin infusion solution (Ribocarbo®-L) showed that besides carboplatin and CBDCA hydrophilic as well as hydrophobic decomposition products are formed during the time of storage. A comparative study using conditions according to the European Pharmacopoeia 1997 (Nucleosil-120-7 NH2-column, acetonitril/water 90/10 (V/V), isocratic conditions at a flow rate of 1.98 ml/min), indicated in the same solution carboplatin in a purity of 100%. Admixture of CBDCA (0.75 mg/ml) could not be detected in the chromatogram, so this investigation gives rise to the assumption that the conditions of the European Pharmacopoeia 1997 are not suitable for carboplatin purity analyses.