Characterization of methotrexate recovered from the urine of high dose patients for the purpose of clinical re-use

A. Leyva, P. D. Baygell, A. C. van Loenen, P. van Asten, C. Pintus, F. Spreafico, H. M. Pinedo

Research output: Contribution to journalArticlepeer-review

Abstract

High dose methotrexate (MTX) therapy with leucovorin rescue is now frequently used in cancer chemotherapy especially in the adjuvant treatment of osteogenic sarcoma. Due to the large quantities of MTX required the cost of this therapy has limited its use in many European oncology centers. Since as much as 90% of the MTX dose is excreted largely unmetabolized in the urine during the first 24 hr following administration, the possibility of the recovery of the drug for re-use was investigated. From the urine of patients having received 10-18 g MTX, at least 50% of the initial dose was recovered for clinical re-utilization. MTX was purified from urine primarily by acid precipitation. Calcium phosphate treatment and ultrafiltration in the purification procedure were used for the removal of pyrogens. The urine-derived drug preparation was 90-95% MTX based on absorbance at 260 nm after fractionation on DEAE cellulose and contained impurities with spectral properties characteristic of pteridine compounds as found in the commercial drug. Most of the impurities detected in the recovered MTX were similar to those in the commercial drug with respect to chromatographic behavior and ultraviolet spectrum. Three new impurities detected in the recovered drug appeared to include the 7-hydroxy-metabolite of MTX. Uric acid was also present as a contaminant at a level of approximately 1%. Urinederived MTX inhibited dihydrofolate reductase in vitro and was effective in tumor-bearing mice to a degree equivalent to commercial MTX. Two patients were treated with MTX isolated from urine resulting in favorable antitumor response and no adverse reaction.

Original languageEnglish (US)
Pages (from-to)1017-1028
Number of pages12
JournalEuropean Journal of Cancer (1965)
Volume14
Issue number10
DOIs
StatePublished - 1978
Externally publishedYes

ASJC Scopus subject areas

  • Oncology

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