Measurement of total boron and ¹⁰B concentration and the detection and measurement of elevated ¹⁰B levels in biological samples by inductively coupled plasma mass spectrometry using the determination of ¹⁰B:¹¹B ratios

Abstract

Methods were developed to determine total B and ¹⁰B content in various biological samples, media and reagents by ICP-MS. Open vessel, wet ash digestion protocols using HNO₃ were developed for the biological and media samples. Digestion of blood and plasma also required H₂SO₄. Despite relatively high blanks, instrumental detection limits using 3σ at or near the blank level were, for total boron (total B), <0.1 µmol l^–1 (<1 µg l^–1), and for ¹⁰B, <0.01 µmol l^–1 (<0.1 µg l^–1). Problems with variable blanks, matrix suppression and peak overlap by ¹²C on ¹¹B are discussed. The developed methods were used to analyse samples for a collaborative study with Clinical Neurosciences at Southampton General Hospital, related to boron neutron capture therapy of brain tumours, of the uptake of ¹⁰B by tumour cells in vitro, using tissue culture, and in vivo, in the rat. Detection limits achieved in cells solubilised in 1 M NaOH and medium were <0.001 µmol ml^–1 total B and <0.0001 µmol ml^–110B and, for blood, 0.002 µmol g^–1 total B and 0.0002 µmol g^–110B, ∼10^–9 M boronophenylalanine solutions. The analytical precision for duplicate analyses gave mean within-run RSDs of ∼7% for ¹⁰B concentration and <10% for total B concentration. The determination of ¹⁰B:¹¹B ratios enabled statistically significant increases in ¹⁰B concentration to be detected and confirmed at low B levels where sample digests and digest blanks had similar B contents. Running ¹⁰B:¹¹B ratios for standard and sample solutions were utilised for novel methods of calculating elevated ¹⁰B levels in the samples. Despite achieving low detection limits, elevated ¹⁰B levels could not be confirmed without the determination of ¹⁰B:¹¹B ratios.

References

1. Handbook of Inductively Coupled Plasma Mass Spectrometry, ed. K. E. Jarvis, A. L. Gray and R. S. Houk, Blackie, Glasgow, 1992, p. 341.
2. D. N. Slatkin, Brain, 1991, 114, 1609.
3. A. Mill, New Sci., 18 Nov., 1989, No. 1691, 56.
4. M. Javid, G. L. Brownell and W. H. Sweet, J. Clin. Invest., 1952, 31, 603.
5. H. B. Locksley and L. E. Farr, J. Pharmacol. Exp. Ther., 1955, 114, 484.
6. W. H. Sweet, A. H. Soloway and G. L. Brownell, Acta Radiol., 1963, 1, 114.
7. A. H. Soloway, H. Hatanaka and M. A. Davis, J. Med. Chem., 1967, 10, 714.
8. R. L. Jr. Sneath, J. E. Wright, A. H. Soloway, S. M. O'Keefe, A. S. Dey and W. D. Smolnycki, J. Med. Chem., 1976, 19, 1200.
9. M. Tsuji, M. Ichihashi and Y. Ishima, Jpn. J. Dermatol., 1983, 93, 773.
10. Y. Mishima, C. Honda, M. Ichihashi, H. Obara, J. Hiratsuka, H. Fukada, H. Karashima, T. Kobayashi, K. Kanda and K. Yoshino, Lancet, 1989, 2, 388.
11. Y. Mishima, M. Ichihashi, M. Tsuji, S. Hatta, M. Ueda, C. Honda and T. Suzuki, J. Invest. Dermatol., 1989, 92, 321S.
12. J. A. Coderre, J. Kalef-Ezra, R. G. Fairchild, P. L. Micca, L. E. Reinstein and J. D. Glass, Cancer Res., 1988, 48, 6313.
13. J. A. Coderre, J. D. Glass, S. Packer, P. L. Micca and D. Greenberg, Pigm. Cell Res., 1990, 3, 310.
14. S. Packer, J. A. Coderre, S. Saraf, R. Fairchild, J. Hansrote and H. Perry, Invest. Ophthalmol. Vis. Sci., 1992, 33, 137.
15. K. Z. Matalka, M. Q. Bailey, R. F. Barth, A. E. Staubus, D. M. Adams, A. H. Soloway, S. M. James and J. H. Goodman, in Progress in Neutron Capture Therapy for Cancer, eds. B. Allen, D. Moore and B. Harrington, Plenum Press, New York, 1992, p. 429.
16. B. J. Allen, J. K. Brown, M. H. Mountford, S. R. Tamat, A. Patwardan, D. E. Moore, M. Ichihashi, Y. Mishima and S. B. Kahl, Strahlenther. Onkol., 1989, 165, 163.
17. O. Leukhart, M. Caviezel, A. Eberle, E. Escher and A. Tun-khi, Helv. Chim. Acta, 1976, 59, 2184.
18. M. F. Hawthorne, R. J. Wiersema and M. Takasugi, J. Med. Chem., 1972, 15, 449.
19. R. F. Barth, A. H. Soloway, R. G. Fairchild and R. M. Brugger, Cancer, 1992, 70, 2995.
20. G. Köhler and C. Milstein, Nature (London), 1975, 256, 495.
21. R. G. Fairchild, D. Gabel, B. Laster, D. Greenberg, W. Kiszenick and P. L. Micca, Med. Phys., 1986, 13, 50.
22. W. B. Clarke, M. Koekebakker, R. D. Barr, R. G. Downing and R. F. Fleming, Appl. Radiat. Isotop., 1987, 38, 735 Int. J. Radiat. Appl. Instrum., Part A.
23. D. E. Moore, J. Pharm. Biomed. Anal., 1990, 8, 547.
24. K. Yoshino, M. Okamoto, H. Kakihana, T. Nakanishi, M. Ichihashi and Y. Mishima, Anal. Chem., 1984, 56, 839.
25. F. Salinas, A. M. Pena, J. A. Murillo and J. C. J. Sanchez, Analyst, 1987, 112, 913.
26. C. J. Cook, S. V. Dubiel and W. A. Hareland, Anal. Chem., 1985, 57, 337.
27. W. B. Clarke, C. E. Webber, M. Koekebakker and R. D. Barr, J. Lab. Clin. Med., 1987, 109, 155.
28. S. R. Tamat, D. E. Moore and B. J. Allen, Anal. Chem., 1987, 59, 2161.
29. W. F. Bauer, D. A. Johnson, S. M. Steele, K. Messick, D. L. Miller and W. A. Propp, Strahlenther. Onkol., 1989, 165, 176.
30. D. C. Gregoire, Anal. Chem., 1987, 59, 2479.
31. F. G. Smith, D. R. Wiederin, R. S. Houk, C. B. Egan and R. E. Serfass, Anal. Chim. Acta, 1991, 248, 229.
32. S. Evans and U. Krähenbühl, J. Anal. At. Spectrom., 1994, 9, 1249.
33. H. Vanhoe, R. Dams, C. Vandecasteele and J. Versieck, Anal. Chim. Acta, 1993, 281, 401.
34. S. Evans and U. Krähenbühl, Fresenius' J. Anal. Chem., 1994, 349, 454.
35. A. M. S. Nyomura, R. N. Sah, P. H. Brown and R. O. Miller, Fresenius' J. Anal. Chem., 1997, 357, 1185.
36. T. U. Probst, N. G. Berryman, P. Lemmen, L. Weissfloch, T. Auberger, D. Gabel, J. Carlsson and B. Larsson, J. Anal. At. Spectrom., 1997, 12, 1115.
37. H. P. Schwartz, E. K. Agyel and C. C. McMullen, Earth Planet. Sci. Lett., 1969, 6, 1.
38. M. Shima, J. Geophys. Res., 1963, 67, 911.
39. Handbook of Geochemistry, ed. K. H. Wedepohl, Springer Verlag, New York, 1969.
40. A. J. Spivack and J. M. Edmond, Anal. Chem., 1986, 58, 31.
41. D. C. Gregoire, J. Anal. At. Spectrom., 1990, 5, 623.
42. R. S. Houk, Anal. Chem., 1986, 58, 97A.
43. I. L. Shuttler and H. T. Delves, Analyst, 1986, 111, 651.
44. F. Vanhaecke, H. Vanhoe, C. Vandecasteele and R. Dams, Anal. Chim. Acta, 1991, 244, 115.
45. D. C. Gregoire, Appl. Spectrosc., 1987, 41, 897.
46. D. C. Gregoire, Spectrochim. Acta, Part B, 1987, 42, 895.
47. A. L. Gray and A. R. Date, Analyst, 1983, 108, 1033.
48. D. J. Douglas and R. S. Houk, Prog. Anal. At. Spectrosc., 1985, 8, 1.