Abstract |
Gamma-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-gamma-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 microM 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.
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Authors | H Su, T L Chen, F H Hausheer, E K Rowinsky |
Journal | Journal of chromatography. B, Biomedical sciences and applications
(J Chromatogr B Biomed Sci Appl)
Vol. 695
Issue 2
Pg. 401-8
(Aug 01 1997)
ISSN: 1387-2273 [Print] Netherlands |
PMID | 9300877
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 7-hydroxy-gamma-methylene-10-deazaaminopterin
- Antineoplastic Agents
- Pterins
- gamma-methylene-10-deazaaminopterin
- Aminopterin
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Topics |
- Aminopterin
(analogs & derivatives, blood, therapeutic use)
- Antineoplastic Agents
(blood, therapeutic use)
- Chromatography, High Pressure Liquid
- Humans
- Neoplasms
(blood, drug therapy)
- Pterins
(blood)
- Reproducibility of Results
- Sensitivity and Specificity
- Spectrometry, Fluorescence
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