HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Detection by high-performance liquid chromatography of methotrexate and its metabolites in tumor tissue from osteosarcoma patients treated with high-dose methotrexate/leucovorin rescue.

Abstract
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.
AuthorsL L Samuels, A Feinberg, D M Moccio, F M Sirotnak, G Rosen
JournalBiochemical pharmacology (Biochem Pharmacol) Vol. 33 Issue 17 Pg. 2711-4 (Sep 01 1984) ISSN: 0006-2952 [Print] England
PMID6205660 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Peptides
  • Polyglutamic Acid
  • methotrexate polyglutamate
  • Leucovorin
  • Methotrexate
Topics
  • Chromatography, High Pressure Liquid
  • Humans
  • Leucovorin (therapeutic use)
  • Methotrexate (analogs & derivatives, analysis, metabolism)
  • Osteosarcoma (drug therapy, metabolism)
  • Peptides (analysis)
  • Polyglutamic Acid (analogs & derivatives, analysis)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: