Platinum-specific detection and quantification of oxaliplatin and Pt(R,R-diaminocyclohexane)Cl2 in the blood plasma of colorectal cancer patients

Virginia Ip; Mark J. McKeage; Paul Thompson; Dragan Damianovich; Michael Findlay; Johnson J. Liu

doi:10.1039/B716925F

Platinum-specific detection and quantification of oxaliplatin and Pt(R,R-diaminocyclohexane)Cl₂ in the blood plasma of colorectal cancer patients†

Virginia Ip,^a Mark J. McKeage,^a Paul Thompson,^b Dragan Damianovich,^b Michael Findlay^c and Johnson J. Liu*^a

* Corresponding authors

^a Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
E-mail: j.liu@auckland.ac.nz
Fax: +64 9 3737556
Tel: +64 9 3737599 ext. 86945

^b Department of Oncology, Auckland City Hospital, Auckland, New Zealand

^c Discipline of Oncology, School of Medical Sciences, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand

Abstract

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 = 0.9974), intra- and inter-assay accuracy (101–107%) and precision (3.30–7.12%, n = 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.

This article is part of the themed collection: Synchrotron Radiation

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Article information

DOI: https://doi.org/10.1039/B716925F
Article type: Technical Note
Submitted: 01 Nov 2007
Accepted: 22 Feb 2008
First published: 13 Mar 2008

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J. Anal. At. Spectrom., 2008,23, 881-884

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Platinum-specific detection and quantification of oxaliplatin and Pt(R,R-diaminocyclohexane)Cl₂ in the blood plasma of colorectal cancer patients

V. Ip, M. J. McKeage, P. Thompson, D. Damianovich, M. Findlay and J. J. Liu, J. Anal. At. Spectrom., 2008, 23, 881 DOI: 10.1039/B716925F

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Journal of Analytical Atomic Spectrometry