A validated inductively coupled plasma mass spectrometry (ICP-MS) method for the quantification of total platinum content in plasma, plasma ultrafiltrate, urine and peritoneal fluid

Abstract

Oxaliplatin is a platinum (Pt)(1) containing antineoplastic agent that is applied in current clinical practice for the treatment of colon and appendiceal neoplasms. A fully validated, highly sensitive, high throughput inductively coupled plasma mass spectrometry (ICP-MS) method is provided to quantify the total Pt content in plasma, plasma ultrafiltrate, urine and peritoneal fluid. In this ICP-MS approach, the only step of sample preparation is a 1000-fold dilution in 0.5% nitric acid, allowing the analysis of 17 samples per hour. Detection of Pt was achieved over a linear range of 0.01-100 ng/mL. The limit of quantification was 18.0 ng/mL Pt in plasma, 8.0 ng/mL in ultrafiltrate and 6.1 ng/mL in urine and peritoneal fluid. The ICP-MS method was further validated for inter-and intraday precision and accuracy (<= 15%), recovery, robustness and stability. Short-term storage of the biofluids, for 14 days, can be performed at -4 degrees C, -24 degrees C and -80 degrees C. As to long-term stability, up to 5 months, storage at -80 degrees C is encouraged. Furthermore, a timeline assessing the total and unbound Pt fraction in plasma and ultrafiltrate over a period of 45 h is provided. Following an incubation period of 5 h at 37 degrees C, 19-21% of Pt was recovered in the ultrafiltrate, emphasizing the extensive and rapid binding of oxaliplatin-derived Pt to plasma proteins. The described method can easily be implemented in a routine setting for pharmacokinetic studies in patients treated with oxaliplatin-based hyperthermic intraperitoneal perioperative chemotherapy. (C) 2018 Elsevier B.V. All rights reserved.