Additional Impurities Identified in Borocaptate Sodium

  • W. F. Bauer
  • G. L. Gresham
  • A. K. Gianotto

Abstract

Reliable quality control has long been an issue with the production of borocaptate sodium (BSH) because of the toxicity associated with the degradation products of BSH1,2. The quality control issues have largely centered around the oxidation of BSH to the dimer, BSS, and oxidized dimer BSSO. A typical determination of the “purity” of the BSH drug primarily identifies the oxidation products and some reaction intermediates by high pressure liquid chromatography (HPLC)1,3. Occasionally, the HPLC chromatograms of BSH show additional peaks which result from compounds that have not yet been identified3. Because the quality control analyses are performed on most BSH prior to it’s use, there should be a reasonable level of confidence that BSH can be administered safely, even at relatively high concentrations if the oxidation products are the primary causes of toxicity. In practice, some toxic effects have been noted in human patients administered BSH at high doses including nausea4, chest pain4,5, and flushed faces5. Recent work has indicated that high doses of BSH caused several cardiac abnormalities in rats6. Five dogs unexpectedly died during, or soon after, the administration of 10BSH at a dose of 100 mg 10B/kg body weight. In a follow up study, an instrumented dog was administered BSH at a dose of 555 mg B/kg without fatal cardiotoxicity although some cardiac effects were observed7.

Keywords

High Pressure Liquid Chromatography Thermal Desorption Carbon Disulfide Head Space Carbonyl Sulfide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    T. Yoshizaki, I. Ikeuchi, and K. Nagasawa, Quality control of Na, 10B12H11SH for neutron capture therapy, in: “Neutron Capture Therapy,” H. Hatanaka, ed., Nishimura Co., Ltd., Niigata, Japan. 1986, pp. 394–400.Google Scholar
  2. 2.
    D.D. Joel, E.N. Slatkin, P.L. Micca, M.M. Nawrocky, T. Dubois and C. Velez, Uptake of boron into human gliomas of athymic mice and into syngeneic cerebral gliomas of rats after intracarotid infusion of sulfhydryl boranes, in: “Clinical Aspects of Neutron Capture Therapy,” R. Fairchild, V. Bond and A. Woodhead, eds., Plenum Press, New York, 1989, pp. 325–332.CrossRefGoogle Scholar
  3. 3.
    A.K. Gianotto and W.F. Bauer, Purity and quality determinations of borocaptate sodium, in:- “Advances in Neutron Capture Therapy,” A.H. Soloway, R.F. Barth and D.E. Carpenter. eds., Plenum Press, New York, 1993, pp. 459–463.Google Scholar
  4. 4.
    G. Stragliotto, D. Schüpbach, P.R. Gavin, and H. Fankhauser, Update on biodistribution of borocaptate sodium (BSH) in patients with intracranial tumors, in: “Advances in Neutron Capture Therapy,” A.H. Soloway, R.F. Barth and D.E. Carpenter, eds., Plenum Press. New York, 1993, pp. 459–463.Google Scholar
  5. 5.
    H. Hatanaka, K. Amano, H. Kanemitsu, I. Ikeuchi, and T. Yoshizaki, Boron uptake by human brain tumors and quality control of boron compounds,“ Chapter V in: ”Boron-Neutron Capture Therapy for Tumors.“ H. Hatanaka, ed., Nishimura Co., Ltd., Niigata, Japan, 1986, pp 77–106.Google Scholar
  6. 6.
    T. Lahann, Pharmacology and toxicology of BSH, in: “INEL BNCT Research Program Annual Report, 1993,” J.R. Venhuizen, ed., INEL, Idaho Falls, EGG-2738, 1994, pp. 46–54.Google Scholar
  7. 7.
    M.P. Moore, C.D. Swartz, P.R. Gavin and R. Bagley, Evaluation of potential toxic effects of borocaptate sodium (BSH) in beagle dogs - a pilot study, Abstract 159 presented at the Sixth International Symposium on Neutron Capture Therapy for Cancer, Kobe, Japan, October 2I-November 4, 1994.Google Scholar
  8. 8.
    N.I. Sax and R.J. Lewis, “Dangerous Properties of Industrial Materials,” Seventh Edition, Van Nostrand Reinhold, New York, 1989.Google Scholar
  9. 9.
    T. Nakagawa and T. Nagai, Interaction between serum albumin and mercaptoundecahydrododecaborate Ion (an agent for boron-neuron capture therapy of brain tumor), I. Introductory remarks and preliminary experiments, Chem. Pharm. Bull. 24: 2934–2941, 1976.PubMedCrossRefGoogle Scholar
  10. 10.
    E.I. Tolpin, G.R. Wellum and S.A. Berley, Synthesis and Chemistry of Mercaptoundecahydro-closo-dodecaborate(2-), Inorg. Chem. 17: 2867–2873, 1978.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • W. F. Bauer
    • 1
  • G. L. Gresham
    • 1
  • A. K. Gianotto
    • 1
  1. 1.Idaho National Engineering LaboratoryLITCOIdaho FallsUSA

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