Novel high-performance liquid chromatographic assay using fluorescence detection for the quantitation of plasma γ-methylene-10-deazaaminopterin and its major metabolite, 7-hydroxy-γ-methylene-10 -deazaaminopterin, in patients with solid cancers in a phase I trial

H. Su, T. L. Chen, F. H. Hausheer, E. K. Rowinsky

Research output: Contribution to journalArticlepeer-review

Abstract

γ-Methylene-10-deazaaminopterin (MDAM), a unique dihydrofolate reductase inhibitor, has demonstrated antitumor activity against a broad spectrum of human solid tumors in preclinical studies. A novel reversed-phase, ion-pair high-performance liquid chromatography (HPLC) assay that uses fluorescence detection has been developed to quantitate levels of MDAM and its major metabolite, 7-hydroxy-γ-methylene-10-deazaaminopterin (7-OH-MDAM), in human plasma. The recovery of MDAM and 7-OH-MDAM from plasma was >97% by a simple one-step deproteinization process using tetrabutylammonium bromide (TBABr) and methanol. MDAM and 7-OH-MDAM remained stable in plasma over a 28-day test period at ambient temperatures, and neither compound was light-sensitive. The limit of quantitation was 0.005 μM for both MDAM and 7-OH-MDAM. This assay has been found to be simple, sensitive and reproducible in determining plasma concentrations of MDAM and 7-OH-MDAM in patients with solid cancers in a phase trial.

Original languageEnglish (US)
Pages (from-to)401-408
Number of pages8
JournalJournal of Chromatography B: Biomedical Applications
Volume695
Issue number2
DOIs
StatePublished - Aug 1 1997
Externally publishedYes

Keywords

  • γ-Methylene-10-deazaaminopterin
  • 7-hydroxy-γ-methylene-10-deazaaminopterin

ASJC Scopus subject areas

  • Chemistry(all)

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