University of Tasmania
Browse

File(s) under permanent embargo

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

journal contribution
posted on 2023-05-17, 22:32 authored by Ip, V, McKeage, MJ, Thompson, P, Damianovich, D, Findlay, M, Johnson Liu
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.

History

Publication title

Journal of Analytical Atomic Spectrometry

Volume

23

Pagination

881-884

ISSN

0267-9477

Department/School

School of Pharmacy and Pharmacology

Publisher

UK

Place of publication

R S C Publications

Rights statement

Copyright 2008 The Royal Society of Chemistry

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

Usage metrics

    University Of Tasmania

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC