Oxaliplatin is a medically-important platinum-based drug for treating advanced colorectal cancer, but its clinical pharmacokinetics and biotransformation are not well understood. We report the development of a reliable sample preparation procedure and a specific HPLC-ICP-MS assay for oxaliplatin and its putative active biotransformation product Pt(R,R-diaminocyclohexane)Cl2 [Pt(DACH)Cl2], and their application to the analysis of the plasma of patients undergoing a standard 2 h infusion of oxaliplatin. HPLC conditions were identified for separating intact oxaliplatin and Pt(DACH)Cl2 that were compatible with on-line detection by ICP-MS. Plasma samples were processed immediately after collection by methanol deproteinization, then stored under conditions in which the analytes of interest were stable. The linearity of calibration curves (R2 ¼ 0.9974), intra- and inter-assay accuracy (101–107%) and precision (3.30–7.12%, n ¼ 5), drug recovery (95–108%), and short- and long-term stability were adequate to quantify oxaliplatin. Clinical application of the assay showed that intact oxaliplatin was the major active platinum species in the plasma of colorectal cancer patients given oxaliplatin. Pt(DACH)Cl2 was undetectable in patient samples despite the HPLC-ICP-MS assay having a limit of detection of 5 nM (1.9 ppb) for this platinum species.

Item Type:	Refereed Article
Keywords:	platinum anticancer drug, colorectal cancer, ICP-MS
Research Division:	Biomedical and Clinical Sciences
Research Group:	Pharmacology and pharmaceutical sciences
Research Field:	Clinical pharmacology and therapeutics
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Liu, JJ (Dr Johnson Liu)
ID Code:	89124
Year Published:	2008
Web of Science® Times Cited:	17
Deposited By:	Pharmacy
Deposited On:	2014-02-25
Last Modified:	2014-08-05
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