Sensitive species-specific monitoring of a new triplatinum anti-cancer drug and its potential related compounds in spiked human plasma by cation-exchange HPLC-ICP-MS

A sensitive method was developed for the specific determination of a new triplatinum anti-cancer drug (BBR3464) in spiked human plasma in the presence of potentially related compounds. In order to recover the pharmacologically active and the free-circulating drug, two methods of sample preparation, one based on the removal of the covalently protein-bound platinum by acid precipitation, and the other involving the removal of the covalently and the non-covalently protein-bound platinum by ultrafiltration, were optimized, respectively. The analytical method was optimized using human plasma spiked with the native drug and five potentially related compounds. The compounds were baseline separated by cation-exchange HPLC and detected by ICP-MS coupled on-line via a Meinhard nebulizer fitted with a refrigerated cyclonic spray chamber. A preconcentration step by freeze-drying prior to analysis was developed to improve the detection limits down to the 0.15 ng mL-1 (as Pt) level, the lowest ever reported. The analytical method developed was validated according to the criteria in force in the pharmaceutical industry. The precision and accuracy of calibration curve points and quality control samples were below 15% and 20% for the 1-10 ng mL-1 and 0.2-1 ng mL-1 concentration ranges, respectively. © The Royal Society of Chemistry 2003.