LC–MS/MS assay for the quantitation of the ribonucleotide reductase inhibitor triapine in human plasma

Julia Matsumoto, Brian F. Kiesel, Robert A. Parise, Jianxia Guo, Sarah Taylor, Marilyn Huang, Julie L. Eiseman, S. Percy Ivy, Charles Kunos, Edward Chu, Jan H. Beumer

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The ribonucleotide reductase inhibitor and radiosensitizer triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP), NSC 663249) is clinically being evaluated via the intravenous (IV) route for the treatment of cervical and vulvar cancer in combination with primary cisplatin chemoradiation. The need for a 2-h infusion and frequent administration of triapine is logistically challenging, prompting us to pursue oral (PO) administration. In support of the clinical trial investigating oral triapine in combination with chemoradiation, we developed and validated a novel LC–MS/MS assay for the quantification of triapine in 50 μL human plasma. After protein precipitation, chromatographic separation of the supernatant was achieved with a Shodex ODP2 column and an isocratic acetonitrile-water mobile phase with 10% ammonium acetate. Detection with an ABI 4000 mass spectrometer utilized electrospray positive mode ionization. The assay was linear from 3 to 3,000 ng/mL and proved to be accurate (97.1–103.1%) and precise (<7.4% CV), and met the U.S. FDA guidance for bioanalytical method validation. This LC–MS/MS assay will be an essential tool to further define the pharmacokinetics and oral bioavailability of triapine.

Original languageEnglish (US)
Pages (from-to)154-160
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume146
DOIs
StatePublished - Nov 30 2017
Externally publishedYes

Keywords

  • Assay
  • Tandem mass spectrometry
  • Triapine
  • Validation

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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  • Cite this

    Matsumoto, J., Kiesel, B. F., Parise, R. A., Guo, J., Taylor, S., Huang, M., Eiseman, J. L., Ivy, S. P., Kunos, C., Chu, E., & Beumer, J. H. (2017). LC–MS/MS assay for the quantitation of the ribonucleotide reductase inhibitor triapine in human plasma. Journal of Pharmaceutical and Biomedical Analysis, 146, 154-160. https://doi.org/10.1016/j.jpba.2017.08.036