Development and application of inductively coupled plasma mass spectrometry techniques to investigate platinum chemotherapy agents

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Cisplatin (cDDP), the first platinum chemotherapy compound, has been used in cancer chemotherapy in human beings and animals for more than thirty years. Satraplatin (JM216), the first oral-administrated anti-tumor platinum compound, shows potential in treating solid tumors with low toxicity in clinical trials. The first objective of this work was to develop and apply analytical procedures to determine the maximally tolerated dose of satraplatin, its efficacy, safety and pharmacokinetics in dogs. This work also aimed to better understand the mechanism of cisplatin cell resistance by investigating cisplatin uptake in different human embryo kidney (HEK) cells. In this study, a robust and highly sensitivity experimental quadrupole ICP-MS methodology was developed and used to analyze platinum and copper in biological matrices and acid-assistant closed-vessel microwave digestion and heated sonic water bath digestion were used for sample preparation.