Detection by high-performance liquid chromatography of methotrexate and its metabolites in tumor tissue from osteosarcoma patients treated with high-dose methotrexate/leucovorin rescue
| Autor: | Francis M. Sirotnak, Gerald Rosen, L L Samuels, D. M. Moccio, Aaron Feinberg |
|---|---|
| Rok vydání: | 1984 |
| Předmět: |
musculoskeletal diseases
medicine.medical_treatment Metabolite Leucovorin Biochemistry High-performance liquid chromatography chemistry.chemical_compound Column chromatography Dihydrofolate reductase medicine Humans Chromatography High Pressure Liquid Pharmacology Chemotherapy Osteosarcoma Chromatography biology Polyglutamate Chemistry Enzyme assay Methotrexate Polyglutamic Acid biology.protein Peptides medicine.drug |
| Zdroj: | Biochemical pharmacology. 33(17) |
| ISSN: | 0006-2952 |
| Popis: | Methotrexate (MTX) polyglutamates were detected in osteogenic sarcoma tumor samples obtained from patients 24 or 48 h after receiving high-dose MTX/leucovorin rescue therapy. Tumor samples were assayed by high-performance liquid chromatography, and polyglutamyl metabolites, along with MTX, were quantitated using both direct u.v. absorption at 313 nm and an enzyme titration assay. Good agreement between these two methods was found although the more sensitive enzyme assay detected peaks in some samples not detected by u.v. absorbance. A wide variation in MTX:MTX polyglutamate levels (1:1 to 25:1) was found among the six clinical samples studied. Also, no correlation between the extent of polyglutamate formation and plasma levels (determined at the time of tumor sampling) was observed. High intracellular levels of a derivative which appears to be the 7-hydroxy metabolite of MTX were also detected in four of six samples. This material coeluted with authentic standard, showed spectral properties like standard 7-OH-MTX, and did not inhibit dihydrofolate reductase. |
| Databáze: | OpenAIRE |
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