Residual Platinum Concentrations in Post-Cancer Chemotherapy and Healthy Control Populations Using an Automated, 96-Well Plate Method and Inductively Coupled Plasma Mass Spectrometry.

Abstract

Platinating agents are among the most commonly used cytotoxic drugs worldwide. It is recognized that Pt concentration can remain significantly increased in serum up to 20 years after completion of chemotherapy, with levels related to late treatment effects. A Freedom EVO® Tecan liquid handler was used for aliquoting 50 μL serum at 10-fold dilution into 96-well plates. The Teledyne MVX-7100 low-volume autosampler was used for sample introduction into an Agilent 7900 inductively coupled plasma mass spectrometry. There was <1.2 min needed between injections. Time to completion for a maximum batch size using two 96-well plates was approximately 3.5 h, including preparation and analysis. Imprecision was <15%, and the limit of quantification was set at 5 ng/L based on imprecision of 18.3%. Bias based on fortified samples ranged from 0% to -4.3% within the analytical measurement range of 5-10 000 ng/L. The nonparametric reference interval for platinum in serum using 147 residual clinical samples was determined to be 8-47 ng/L. Serum platinum concentrations in 675 enrolled patients having an average time since chemotherapy completion of 6.4 (± 5.5 years) ranged from 20.1 to 8252.4 ng/L. Among all patients, 633 (94%) had serum concentrations exceeding 47 ng/L, and 42 (6%) had serum platinum concentrations between 8 and 47 ng/L. This method used an automated liquid handler, a novel 96-well autosampler and 50 μL patient serum to quantify platinum levels. The method was successfully validated according to current clinical guidelines for laboratory developed tests.