Novel assay method for mitoxantrone in plasma, and its application in cancer patients

Oliver Yoa Pu Hu, Shiu Pei Chang, Yn Ben Song, Kuang Yao Chen, Chi Kong Law

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Mitoxantrone is an anthracene derivative that acts as a cytostatic in a variety of cancers. A quantitative analytical method has been established for the determination of mitoxantrone in plasma. The method employed C18 reversed-phase ion-pair chromatography with an isocratic mobile phase of 50.0% methanol in 10 mM phosphate buffer (pH 3.0) plus 0.09% 1-pentanesulphonic acid and ultraviolet detection. Sample preparation consisted of two extraction steps using same organic solvent system at different pH to remove plasma impurities efficiently. Potential adsorption of mitoxantrone onto glassware was considered. Silanization of all glassware with 5% dichlorodimethylsilane in chloroform increased the extraction recovery in plasma from 50 to 85% with high reproducibility. Mitoxantrone was unstable in human plasma. To maintain plasma sample integrity, each millilitre of sample should be fortified with 0.1 ml of 5% vitamin C (in citrate buffer) and kept frozen until analysis. Using this new method, the calibration curve of mitoxantrone in plasma in the range of interest (1-500 ng/ml) showed good linearity (r = 0.996) and precision (both between-day and within-day coefficients of variation less than 10%). The lower detection limit of this assay method was 1 ng. The application of this method allowed us to study the stability of mitoxantrone in plasma, and the pharmacokinetics of mitoxantrone in nasopharyngeal carcinoma patients receiving 12 mg/m2. The study revealed a prolonged terminal phase half-life for mitoxantrone.

Original languageEnglish
Pages (from-to)337-350
Number of pages14
JournalJournal of Chromatography B: Biomedical Sciences and Applications
Volume532
Issue numberC
DOIs
Publication statusPublished - Jan 1 1990
Externally publishedYes

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Mitoxantrone
Assays
Plasmas
Buffers
Plasma (human)
Ion chromatography
Pharmacokinetics
Cytostatic Agents
Chloroform
Citric Acid
Organic solvents
Ascorbic Acid
Methanol
Phosphates
Calibration
Impurities
Derivatives
Adsorption
Recovery

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Novel assay method for mitoxantrone in plasma, and its application in cancer patients. / Hu, Oliver Yoa Pu; Chang, Shiu Pei; Song, Yn Ben; Chen, Kuang Yao; Law, Chi Kong.

In: Journal of Chromatography B: Biomedical Sciences and Applications, Vol. 532, No. C, 01.01.1990, p. 337-350.

Research output: Contribution to journalArticle

Hu, Oliver Yoa Pu ; Chang, Shiu Pei ; Song, Yn Ben ; Chen, Kuang Yao ; Law, Chi Kong. / Novel assay method for mitoxantrone in plasma, and its application in cancer patients. In: Journal of Chromatography B: Biomedical Sciences and Applications. 1990 ; Vol. 532, No. C. pp. 337-350.
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