Species specific IDMS for accurate quantification of carboplatin in urine by LC-ESI-TOFMS and LC-ICP-QMS

Abstract

For the first time, ¹⁹⁴Pt isotopically enriched carboplatin has been synthesized, serving for species specific isotope dilution analysis. Carboplatin was determined in urine, implementing both LC-ICP-QMS and LC-ESI-TOFMS. Hence, a separation method was applied, compatible with both ICP-QMS and ESI-MS detection. IDMS quantification was evaluated in terms of measurement uncertainty, comparing the two mass spectrometric detection methods. The procedural limits of detection of HPLC-ICP-QMS and HPLC-ESI-TOFMS were 0.1 ng g^–1 and 15 ng g^–1, respectively. Both methodologies were successfully applied to the quantification of carboplatin in the urine of a chemotherapy patient. The obtained carboplatin concentrations agreed within their uncertainties. Uncertainty budgeting calculations revealed that the accuracy of quantification was primarily limited by the precision of isotope ratio measurement, governing the determination of the ratios R_x, R_y and R_b of the IDMS equation. For ICP-QMS, a total combined uncertainty of 5.7% (coverage factor 2) was assessed. In accordance to the impaired precision of blend ratio determination in ESI-TOFMS (precision of 5% compared to 1% in ICP-QMS), this method revealed a total combined uncertainty of 23%.