High-Performance Liquid Chromatography of Iproplatin, an Antitumor Quadrivalent Platinum Complex

Abstract

Iproplatin [cis-dichloro-trans-dihydroxo-bis(isopropylamine)platinum(IV), CHIP] is a potent antitumor platinum complex with axial hydroxy ligands. The high-performance liquid chromatographic behavior of CHIP was investigated on a poly(styrene-divinylbenzene)-based cation exchange column with a dipotasshim hydrogen phosphate eluent and an octadecylsilica column with a phosphate buffer/methanol eluent containing a sodium alkylsulfonate. On both cation exchange and octadecylsilica columns, the capacity factor of CHIP increased, the lower was the eluent pH. However, this was not found to be the case in the absence of an alkylsulfonate. Using the cation exchange column, the CHIP capacity factors at various pH values were plotted (on log-log graph paper) as a function of the eluent potassium concentration. Straight lines were obtained with slopes of —0.65 at pH 4.0 and —0.81 at pH 2.5. The observed charges on CHIP evaluated from these slopes were 0.65 at pH 4.0 and 0.81 at pH 2.5, indicating that a large portion of CHIP was present as a monovalent cation in both cases. This study shows that CHIP is protonated and, consequently, can be chromatographed on cation exchange and octadecylsilica columns as a cationic compound, under acidic conditions.