Summary
Gas chromatographic-mass spectrometric techniques were developed for the identification and quantification of pyrazofurin, orotic acid, and orotidine in human serum and urine. Free pyrazofurin was detected for the first time in both the serum and urine of patients receiving the drug. Plasma clearance studies established that the level of pyrazofurin decays exponentially with a half-life of the distribution phase of approx. 10 min. Urinary excretion yields only 10% of the total drug administered (in 10 days). Orotic acid and orotidine were positively identified in urine; quantification revealed that 20–100 mmole of orotic acid and 40–80 mmole of orotodine are excreted in a period of 8-10 days. Pyrazofurin 5’-phosphate was identified for the first time in cells (both T and B type) incubated with pyrazofurin. These findings together with the results of reversal experiments support the assumption that the mode of operation of the drug is the interruption of the conversion of orotidine 5’-monophosphate to uridine 5’-monophosphate in the course of the biosynthesis of pyrimidine nucleotides.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
R.H. Williams, K. Gerson, M. Hoehn, J. Gorman and D.C. DeLong, in “158th Amer.Chem.Soc.Natl.Mtg., New York, N.Y. (Abstr. MICR 38)”, 1969.
F.J. Streightoff, J.D. Nelson, J.C. Cline, K. Gerson, M. Hoehn, R.H. Williams, M. Gorman and D.C. DeLong, in “Ninth Conference on Antimicrobial Agents and Chemotherapy”, Washington, D.C., 1969, p. 8.
D.C. DeLong, L.A. Baker, K. Gerson, G.E. Gutowski, R.H. Williams and R.L. Hamill, in “Proc. 7th Intern. Congr. of Chemother., Prague, Czechoslovakia”, 1971.
M.J. Sweeney, F.A. Davis, G.E. Gutowski, R.L. Hamill, D.H. Hoffman and G.A. Poore, Cancer Res., 1973, 33, 2619.
G.E. Gutowski, M.J. Sweeney, D.C. DeLong, R.C. Hamill and K. Gerson, Ann. N.Y. Acad. Sci., 1975, 255, 544.
Brochure, Compound 47599, Pyrazofurin, Eli Lilly Co., Indianapolis, Ind., 1973.
Minutes of the Phase I Working Group, Cancer Therapy Evaluation Program, National Cancer Institute, NIH, USA, Oct. 3, 1974 and Feb. 25, 1975.
T. Ohnuma, J. Roboz, M.L. Shapiro and J.F. Holland, Proc. Am. Assoc. Cancer Res. and Am. Soc. Clin. Oncol., 1976, 17, 184.
E.C. Cadman, D.E. Dix, S.C. Hill and R.E. Handshumacher, Proc. Am. Assoc. Cancer Res. and Am. Soc. Clin. Oncol., 1976, 17, 208.
R. Handschumacher, J. Biol. Chem., 1960, 235, 2917.
J. Roboz, R. Suzuki, M. Perloff and T. Ohnuma, in “Proc. 23rd Ann. Conf. Mass Spectrom., Dallas, Texas, 1975.
J.L. Occolowitz, M.R. Gleissner and G.E. Gutowski, personal communication, 1976.
J. Minowada, T. Ohnuma and G.E. Moore, J. Nat. Cancer Inst., 1972, 49, 891.
G.E. Moore, in “Cell lines from human with hematopoietic malignancies in human cells in vitro”, Fogh J., Ed., Plenum Press, N.Y., 1975, p. 299.
T. Ohnuma, unpublished observation.
J. Roboz, R. Suzuki and T. Ohnuma, submitted for publication.
T. Ohnuma and J.F. Holland, Clin. Pharmacol. Ther., 1966, 7, 763.
V.J. Pileggi, J. DiGiorgio and D.R. Wybenga, Clin. Chim. Acta, 1972, 37, 141.
J. Roboz and L. Twanmoh, unpublished results.
R. Handschumacher, personal communication, 1976.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1977 Plenum Press, New York
About this chapter
Cite this chapter
Roboz, J., Ohnuma, T. (1977). Mass Spectrometric Identification and Quantification of Compounds Involved in the Metabolism of Pyrazofurin. In: Frigerio, A., Ghisalberti, E.L. (eds) Mass Spectrometry in Drug Metabolism. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-4151-2_11
Download citation
DOI: https://doi.org/10.1007/978-1-4613-4151-2_11
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-4153-6
Online ISBN: 978-1-4613-4151-2
eBook Packages: Springer Book Archive