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

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 d...

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Bibliographic Details
Published in:Journal of chromatography. B, Biomedical sciences and applications Biomedical sciences and applications, 1997-08, Vol.695 (2), p.401-408
Main Authors: Su a, H, Chen, T.-L, Hausheer, F.H, Rowinsky a, E.K
Format: Article
Language:English
Subjects:
7-hydroxy-γ-methylene-10-deazaaminopterin
Aminopterin - analogs & derivatives
Aminopterin - blood
Aminopterin - therapeutic use
Analysis
Antineoplastic Agents - blood
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Chromatography, High Pressure Liquid
General pharmacology
Humans
Medical sciences
Neoplasms - blood
Neoplasms - drug therapy
Pharmacology. Drug treatments
Pterins - blood
Reproducibility of Results
Sensitivity and Specificity
Spectrometry, Fluorescence
γ-Methylene-10-deazaaminopterin
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Summary: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 μ M 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 I trial.
ISSN:0378-4347
1387-2273
DOI:10.1016/S0378-4347(97)00205-3