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 journalArticle

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

Fingerprint

Methotrexate
Urine
Pharmaceutical Preparations
Pteridines
Pyrogens
DEAE-Cellulose
Drug Compounding
Tetrahydrofolate Dehydrogenase
Leucovorin
Ultrafiltration
Osteosarcoma
Therapeutics
Uric Acid
Neoplasms
Costs and Cost Analysis
Drug Therapy
Acids

ASJC Scopus subject areas

  • Oncology

Cite this

Leyva, A., Baygell, P. D., van Loenen, A. C., van Asten, P., Pintus, C., Spreafico, F., & Pinedo, H. M. (1978). Characterization of methotrexate recovered from the urine of high dose patients for the purpose of clinical re-use. European Journal of Cancer (1965), 14(10), 1017-1028. https://doi.org/10.1016/0014-2964(78)90056-7

Characterization of methotrexate recovered from the urine of high dose patients for the purpose of clinical re-use. / Leyva, A.; Baygell, P. D.; van Loenen, A. C.; van Asten, P.; Pintus, C.; Spreafico, F.; Pinedo, H. M.

In: European Journal of Cancer (1965), Vol. 14, No. 10, 1978, p. 1017-1028.

Research output: Contribution to journalArticle

Leyva, A, Baygell, PD, van Loenen, AC, van Asten, P, Pintus, C, Spreafico, F & Pinedo, HM 1978, 'Characterization of methotrexate recovered from the urine of high dose patients for the purpose of clinical re-use', European Journal of Cancer (1965), vol. 14, no. 10, pp. 1017-1028. https://doi.org/10.1016/0014-2964(78)90056-7
Leyva, A. ; Baygell, P. D. ; van Loenen, A. C. ; van Asten, P. ; Pintus, C. ; Spreafico, F. ; Pinedo, H. M. / Characterization of methotrexate recovered from the urine of high dose patients for the purpose of clinical re-use. In: European Journal of Cancer (1965). 1978 ; Vol. 14, No. 10. pp. 1017-1028.
@article{77347413860c4f2997a21af57a273799,
title = "Characterization of methotrexate recovered from the urine of high dose patients for the purpose of clinical re-use",
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.",
author = "A. Leyva and Baygell, {P. D.} and {van Loenen}, {A. C.} and {van Asten}, P. and C. Pintus and F. Spreafico and Pinedo, {H. M.}",
year = "1978",
doi = "10.1016/0014-2964(78)90056-7",
language = "English (US)",
volume = "14",
pages = "1017--1028",
journal = "European journal of cancer",
issn = "0014-2964",
publisher = "Pergamon Press Ltd.",
number = "10",

}

TY - JOUR

T1 - Characterization of methotrexate recovered from the urine of high dose patients for the purpose of clinical re-use

AU - Leyva, A.

AU - Baygell, P. D.

AU - van Loenen, A. C.

AU - van Asten, P.

AU - Pintus, C.

AU - Spreafico, F.

AU - Pinedo, H. M.

PY - 1978

Y1 - 1978

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0018074368&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018074368&partnerID=8YFLogxK

U2 - 10.1016/0014-2964(78)90056-7

DO - 10.1016/0014-2964(78)90056-7

M3 - Article

C2 - 280457

AN - SCOPUS:0018074368

VL - 14

SP - 1017

EP - 1028

JO - European journal of cancer

JF - European journal of cancer

SN - 0014-2964

IS - 10

ER -