Quantification of cisplatin, carboplatin and oxaliplatin in spiked human plasma samples by ICP-SFMS and hydrophilic interaction liquid chromatography (HILIC) combined with ICP-MS detection

Abstract

Therapeutic drug monitoring addresses the determination of the free and intact drug in patient blood. The free fraction of cancerostatic platinum compounds (CPC) is determined by measurement of total platinum levels in plasma ultrafiltrate. In this work, as a starting point, the distribution of cisplatin, carboplatin and oxaliplatin among different blood compartments, i.e. whole blood, plasma, residue (pellet fraction), plasma-ultrafiltrate and protein-residue fraction, was assessed in an ex vivo experiment via ICP-SFMS measurement of total platinum after microwave digestion. The results clearly showed that the distribution is independent of the initial concentration but dependent on the used drug. The platinum in the plasma-ultrafiltrate amounted to 16.8 ± 1.3%, 56.8 ± 0.1% and 10.4 ± 1.0% for cisplatin, carboplatin and oxaliplatin, respectively. Acetonitrile precipitation of plasma samples delivered corresponding results simplifying and accelerating (5 min vs. 150 min for plasma ultrafiltration and total digestion) sample preparation. This method could be ideally combined with a novel speciation analytical approach using hydrophilic interaction liquid chromatography (HILIC) with ICP-QMS detection. A comparison of the total platinum levels to species selective results revealed that 88.0 ± 12.0% of cisplatin and 106.4 ± 7.7% of carboplatin were present as parent drug, whereas only 34.3 ± 0.4% of oxaliplatin were present in the intact state.