Analytical Quality Control

  • Gertrude Pfeiffer
Part of the Developments in Nuclear Medicine book series (DNUM, volume 4)


Quality control is the sum of all arrangements made to ensure that a product will be safe and suitable for the intended use. But as Kristensen pointed out (1) “Quality is not an absolute term. When setting up recommendations for preparation and quality control, consideration must be given to economy and time available”. First of all governmental regulations have to be met, but there is a lack of official directions concerning radiopharmaceuticals in many countries and the pharmacopoeias are often not up to date. So decisions concerning the degree of quality control required and the setting of limits for impurities, especially in the case of new radiopharmaceuticals must be made by the manufacturers. They are always looking for fast, precise and simple methods for quality control, so that the given specifications can be tested before the product reaches the patient. Another question is responsibility. It is obvious that the responsibility of the manufacturer ends with the delivery of his products to the hospital. All further manipulations, including dispensing of radiopharmaceuticals and the preparation of Technetium-99m compounds from generator and kits is the responsibility of the hospital pharmacy or the nuclear medicine department, wherever this work will be done.


Radiochemical Purity Radionuclidic Purity Radiopharmaceutical Production High Performance Liquid Chromotography Aluminium Aluminium 
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  1. 1.
    Kristensen K. Preparation and control of radiopharmaceuticals in hospitals. Technical Reports Series No 194 IAEA Vienna 1979.Google Scholar
  2. 2.
    Kaspersen FM, Westera G. Radioiodinated o-iodo benzoic acid as impurity in hippuran preparations. Int J Appl Radiat Isotop 1980; 31: 97.CrossRefGoogle Scholar
  3. 3.
    Hauser W, Cavallo L. Measurement and quality assurance of the amount of administered tracer. In Rhodes BA, ed. Quality Control in Nuclear Medicine, SV Mosby, 1977:154.Google Scholar
  4. 4.
    Johnston AS et al. Dose calibrator readings due to radionuclide impurities found in radiopharmaceuticals. Nuclearmedizin 1980; XIX: 1.Google Scholar
  5. 5.
    Radiopharmaceutical Preparations. European Pharmacopoea, 1 975; III: 371ff.Google Scholar
  6. 6.
    Hoppes, DD. Radionuclidic Purity. In Rhodes BA ed. Quality Control in Nuclear Medicine; SV Mosby, 1977:164.Google Scholar
  7. 7.
    Perolat JP. Table de radionucleides. Commissariat à l`energie atomique, Saclay, 1977.Google Scholar
  8. 8.
    Erdtmann G, Soyka, W. The gamma rays of the radionuclides. In Lieser KH ed. Topical presentations in nuclear chemistry, Vol. 7. 1979.Google Scholar
  9. 9.
    Vinberg N, Kristensen K. Comparative evaluation of Tc-99m-generators. Eur J Nucl Med 1976;1: 219.PubMedCrossRefGoogle Scholar
  10. 10.
    Vinberg N, Kristensen K. Fission Mo-99/Tc-99m generators - a study of their performance and quality. Eur J Nucl Med 1980; 5:435.PubMedCrossRefGoogle Scholar
  11. 11.
    Braun H et al. Determination of and pure-emitting impurities in Mo-99/Tc-99m generator eluates. J Radioanalyt Chem 1981; 67:215.CrossRefGoogle Scholar
  12. 12.
    Vlcek J et al. Results of regular study on radionuclidic purity of Tc-99m obtained from Mo-99/Tc-99m generators. Eur J Nucl Med 1979; 4:385.PubMedCrossRefGoogle Scholar
  13. 13.
    Väyrynen T et al. Residual activity of Tc-generators. Eur J Nucl Med 1981; 6:269.PubMedCrossRefGoogle Scholar
  14. 14.
    Sauter P et al. Alpha-aktivität in Technetiumeluaten von Spaltmolybdängeneratoren. In Oeff K, ed. Nuklearmedizin und Biokybernetik, 14. Internat. Jahrestagung der Gesellschaft für Nuklearmedizin, 1978: 609.Google Scholar
  15. 15.
    Johansson L, Mattsson S. Plutonium in Tc-99m pertechnetate for clinical use. J Nucl Med 1980;21:1091PubMedGoogle Scholar
  16. 16.
    Williams CC et al. The accuracy of 99-Molybdeneum assays in 99m-Technetium solutions. Radiology 1981; 138:445.PubMedGoogle Scholar
  17. 17.
    Zehnder P. Bestimmung der Nuklidreinheit von Jod-131 aus der Eigenproduktion IP. EIR-interner vertraulicher Bericht, 1978, K 7701.Google Scholar
  18. 18.
    Krohn K A, Jansholt A. Radiochemical quality control of short lived radiopharmaceuticals. Int J Appl Radiat Isotop 1977; 28:213.CrossRefGoogle Scholar
  19. 19.
    Bayly RJ. Chemical and radiochemical purity. In Rhodes BA, ed. Quality Control in Nuclear Medicine, SV Mosby, 1977:173.Google Scholar
  20. 20.
    Mellish CE. Limits of accuracy in the determination of purity by thin layer and paper chromatography. In “Analytical control of radiopharmaceuticals”, Proceedings of a panel, IAEA, 1 970, PL-336/10: 115.Google Scholar
  21. 21.
    Cohen Y, Besnard M. Analytical methods of radiopharmaceutical quality control. In Subramanian G, Radiopharmaceuticals, SNM, New York 1975:207.Google Scholar
  22. 22.
    Eckelman WC, Levenson SM. Chromatographic purity of Tc-99m compounds. In Rhodes BA, ed. quality Control in Nuclear Medicine, SV Mosby, 1977:197.Google Scholar
  23. 23.
    Pauwels EKJ, Feitsma RIJ. Radiochemical quality control of Tc-99m labelled radiopharmaceuticals. Eur J Nucl Med 1977;2:97.PubMedCrossRefGoogle Scholar
  24. 24.
    Phan The Tran, Wasnich R. Practical Nuclear Pharmacy. In “Practical Nuclear Medicine Series”, Banyan Enterprises, Honolulu, 1979.Google Scholar
  25. 25.
    Health and Welfare Canada. Results of quality control studies of Tc-99m labelled radiopharmaceuticals prepared from kits (1978, 1979). Canada 1982, 82-EHD-75.Google Scholar
  26. 26.
    Strehlau E, Weiland J. Erfahrungen mit der Qualitätskontrolle kommerzieller and eigenmarkierter Radiopharmazeutika. Radiobiol Radiother 1980;21: 376.Google Scholar
  27. 27.
    Heide L et al. Analytik radiochemischer Verunreinigungen in Radiopharmazeutika. Institut für Strahlenhygiene des Bundesgesundheitsamtes, STH-Berichte, Teil I, 1 979: 1 5, Teil II, 1980:7, Teil III 1980:9, Teil IV 1981:65.Google Scholar
  28. 28.
    Srivastava SC et al. Characterization of Tc-99m bone agents (MDP, EHDP) by reverse phase and ion exchange HPLC. J Nucl Med 1981; 22: P-69.Google Scholar
  29. 29.
    Fritzberg AR, Lewis D. HPLC analysis of Tc-99m iminodiacetate hepatobiliary agents and a question of multiple peaks. J Nucl Med 1980; 21:1180.PubMedGoogle Scholar
  30. 30.
    Colombetti LG et al. Rapid determination of oxidation state of unbound Tc-99m and labelling yield in Tc-99m-1 abe11ed radiopharmaceuticals. J Nucl Med 1976 517:805.Google Scholar
  31. 31.
    Majewski W et al. Radiochemical evaluation of commercial iminodiacetate hepatobiliary radiopharmaceuticals. J Nucl Med Technol 1981; 9: 185.Google Scholar
  32. 32.
    Belkas EP, Archimandritis S. Quality control of colloid and particulate Tc-99m labelled radiopharmaceuticals. Eur J Nucl Med 1979; 4: 375.PubMedCrossRefGoogle Scholar
  33. 33.
    Cooper PA, Zimmer AM. Radiochemical purity and stability of commercial Tc-99m stannous DTPA kits using a new chromatographic technique. J Nucl Med 1975; 3:208.Google Scholar
  34. 34.
    Taukulis RA et al. Technical parameters with miniaturized chromatography system. J Nucl Med Technol 1979; 7:19.Google Scholar
  35. 35.
    Williams CC. Radiochemical purity of Tc-99m oxidronate. J Nucl Med 1981; 22:1015.PubMedGoogle Scholar
  36. 36.
    Owunwanne A et al. Factors influencing paper chromatographic analysis of Technetium-99m phosphorous compounds J Nucl Med 1978; 19:534.PubMedGoogle Scholar
  37. 37.
    Gasche W et al. Chromatographic investigations of Tc-99m-MDP and Tc-99-pyrophosphate. J Nucl Med All Sci 1982; 26:148.Google Scholar
  38. 38.
    Mock BH et al. Rapid miniaturized chromatographic quality procedures for Tc-99m radiopharmaceuticals. J Nucl Med 1978; 19:1086.PubMedGoogle Scholar
  39. 39.
    Zimmer AM et al. Rapid miniaturized chromatography for Tc-99m-IDA-agents: comparison with gel chromatography. Eur J Nucl Med 1982;7:88.PubMedCrossRefGoogle Scholar
  40. 40.
    Persson BRR. Gel chromatography column scanning: a method for identification and quality control of Tc-99m-radiopharmaceuticals. In Subramanian G. ed. Radiopharmaceuticals, SNM, New York, 1975:228.Google Scholar
  41. 41.
    Darte I. A comparative investigation of the gel chromatography column scanning method for quality control of Te-99m-methylene disphosphonate. Nuc1earmedizin 1981; 20:51.Google Scholar
  42. 42.
    Van den Brand JAGM et al. A comparative investigation of various Sephadex-G types and Biogel P-10 in the ge1chromatographic analysis of Tc-99m labelled 1-hydroxy-ethylidene-l, 1-diphosphonate. Int J Appl Radiat Isotop 1979;: 30:129.CrossRefGoogle Scholar
  43. 43.
    Darte I et al. Quality control and testing of Tc-99m macroaggregated albumin. Nuclearmedizin 1976; 15:80.Google Scholar
  44. 44.
    Johansen B. Ge1chromatographische Qualitätskontrolle von Tc-99m-Radiopharmazeutika. Radiobiol Radiother 1976; 17:91.Google Scholar
  45. 45.
    Pszona A, Sakowicz A. The influence of citrate ions on the radiochemical purity of Tc-99m human serum albumin. Int J Appl Radiat Isotop 1981; 32: 349.CrossRefGoogle Scholar
  46. 46.
    Vilcek S et al. Analysis of Tc-99m labelled compounds using sorb gel method. Radiochem Radioanalyt Lett 1982; 52: 55.Google Scholar
  47. 47.
    Millar AM et al. An evaluation of 6 kits of Technetium-99m-human serum albumin injection for cardiac blood pool imaging. Eur J Nucl Med 1979; 4: 91.PubMedCrossRefGoogle Scholar
  48. 48.
    McLean OR et al. Quality control procedures for Tc-99m-MAA. Int J Nucl Med Biol 1979; 6:142.PubMedCrossRefGoogle Scholar
  49. 49.
    Vallabhajosula S et al. Radiochemical analysis of Tc-99m human serum albumin with high pressure liquid chromatography. J Nucl Med 1982; 23:326.PubMedGoogle Scholar
  50. 50.
    Russell CD, Majerik JE. Determination of pertechnetate in radiopharmaceuticals by high pressure liquid, thin layer and paper chromatography. Int J Appl Radiat Isotop 1979; 30:753.CrossRefGoogle Scholar
  51. 51.
    Wong SH et al. Quality control studies of Tc-99m labelled radiopharmaceuticals by high performance liquid chromotography. Int J Appl Radiat Isotop 1981; 32:185.CrossRefGoogle Scholar
  52. 52.
    Rosenberg A, Teare FW. A novel rapid thin layer chromatographic monitoring system for the radioiodination of protein and polypeptides. Analyt Biochem 1977; 77:289.PubMedCrossRefGoogle Scholar
  53. 53.
    Siuda A, Lucka, B. Determination of inorganic radioiodine in solutions of I-125–1abe11ed proteins. J Lab comp and radiopharm 1980; 18:915.CrossRefGoogle Scholar
  54. 54.
    Dreyer I et al. Untersuchungen zur Elektrophorese und Papierchromatographie radioaktiv markierter anorganischer Halogenverbindungen im System Dimethylformamid-Ammoniak. Radiochem Radioanalyt Lett 1978; 33: 281.Google Scholar
  55. 55.
    Bögl W, Stockhausen K. Hochdruckflüssigkeits-chromatographische Qualitätskontrolle einiger auf dem Markt befindlicher J-123/J-125/J-131 ortho-jod-Hippurane. Nuclearmedizin 1978; 17:283.Google Scholar
  56. 56.
    Beranek I, Pfeiffer G. Anwendung der Hochleistungs-flüssigchromotographie (HPLC) zur Qualitätskontrolle von Radiopharmaka. EIR-interner Bericht, 1982, TM-52–82-05.Google Scholar
  57. 57.
    Jovanovic V et al. Radiochemical quality control of Tc-99m-labelled radiopharmaceuticals J Radioanalyt Chem 1980; 59:239.CrossRefGoogle Scholar
  58. 58.
    Jovanovic V et al. Determination of radiochemical purity of chlormerodrin-Hg-203 by e1ectrophoretic method. J Radioanalyt Chem 1977; 35:383.CrossRefGoogle Scholar
  59. 59.
    Machulla HJ et al. Radioanalytical quality control of C-11, F-18 and 1–123 labelled compounds and radiopharmaceuticals. J Radioanalyt Chem 1976; 32:381.CrossRefGoogle Scholar
  60. 60.
    Bayly RJ. Chemical and radiochemical purity. In Rhodes BA, ed. Quality Control in Nuclear Medicine, Sv Mosby 1977:173.Google Scholar
  61. 61.
    Shukla SK et al. Effect of aluminium impurities in the generator produced pertechnetate-99m ion on thyroid scintigrams. Eur J Nucl Med 1977; 2:137.PubMedCrossRefGoogle Scholar
  62. 62.
    Zimmer AM, Pavel DG. Experimental investigations on the possible cause of liver appearance during bone scanning. Radiology 1978; 126:813.PubMedGoogle Scholar
  63. 63.
    Müller T, Steinnes E. On the purity of eluates from Tc-99m-generators. Scand J clin lab invest 1971; 28:213.PubMedCrossRefGoogle Scholar
  64. 64.
    Hambright P et al. Rapid spot test for stannous tin levels in Tc-99m kits. J Nucl med Technol 1977; 5:88.Google Scholar
  65. 65.
    Zimmer AM, Spies SM. The paper spot test: a rapid method for quantitaing stannous concentrations in radiopharmaceutical kits. J Nucl Med 1981; 22 : 465.PubMedGoogle Scholar
  66. 66.
    Lin TH et al. Instant spot test for SN (II) in Tc-99m radiopharmaceuticals and kit reagents. J Nucl Med 1981; 22:P-72.Google Scholar
  67. 67.
    Study KT. Determination of stannous ion content on radiopharmaceutical kits using N-bromosuccinimide. J Nucl Med Technol 1982;10:161.Google Scholar
  68. 68.
    McBride MHD et al. Stannous ion quantitation in pyrophosphate and polyphosphate radiopharmaceutical kits using differential pulse polarography. J Pharmaceut Science 1977; 66:870.CrossRefGoogle Scholar
  69. 69.
    Liebscher I et al. Sn (II) Bestimmung in Tc-99m-Sn-DMSA. Radiochem Radioanalyt Lett 1979;37:313.Google Scholar
  70. 70.
    Colombetti LE, Barnes WE. Effect of chemical and radiochemical impurities from eluants on Tc-99m labelling efficiency. Nuclearmedizin 1977; 16:271.Google Scholar
  71. 71.
    Chervu LR et al. Stannous ion quantitation in Tc-99m radiopharmaceutical kits. Eur J Nucl Med 1982; 7:291.PubMedCrossRefGoogle Scholar
  72. 72.
    Study KT et al. The effect of bacteriostatic saline on Tc-99m labelled radiopharmaceuticals. J Nucl Med Technol 1981; 9:115.Google Scholar
  73. 73.
    Study KT et al. Acceptance testing of Thallium-201. J Nucl Med 1979; 20: 684.Google Scholar
  74. 74.
    Waxman AD et al. Are all Gallium citrate preparations the same? Radiology 1975; 117: 647.PubMedGoogle Scholar
  75. 75.
    Bremer KH. Herstellung und in vitro Stabilität der Testsubstanzen für Nierenuntersuchungen. In Höfer R, ed. Nierenclearance, Hoechst, 1968/69.Google Scholar
  76. 76.
    Krogsgaard OW. Technetium-99m sulfur colloid. Eur J Nucl Med 1976; 1: 31.PubMedGoogle Scholar
  77. 77.
    Pedersen B, Kristensen K. Evaluation of methods for sizing of colloidal radiopharmaceuticals. Eur J Nucl Med 1981; 6: 521.PubMedGoogle Scholar
  78. 78.
    Warbick A et al. An evaluation of radiocolloid sizing techniques. J Nucl Med 1977; 18:827.PubMedGoogle Scholar
  79. 79.
    Billinghurst MW, Jette D. Colloidal particle size determination by gel filtration. J Nucl Med 1979; 20:133.PubMedGoogle Scholar
  80. 80.
    Persson BRR et al. Radioana1ytica1 studies of Tc-99m labelled colloids and macromolecules with gel chromatography column scanning technique. J Radioanalyt Chem 1978; 43:275.CrossRefGoogle Scholar
  81. 81.
    Servian JL. Report of an international atomic energy agency meeting on quality control of radiopharmaceuticals. Int J Appl Radiat Isotop 1977;28:653.CrossRefGoogle Scholar
  82. 82.
    Gopal NGS et al. Radiometric sterility test for radiopharmaceuticals. Isotopenpraxis 1976; 12:257.CrossRefGoogle Scholar
  83. 83.
    Rhodes BA. Radiometric sterility testing. In Rhodes BA, ed. Quality Control in Nuclear Medicine, CV Mosby, 1977:226.Google Scholar
  84. 84.
    Sørensen K et al. Microbial contamination of radionuclide generators. Eur J Nucl Med 1977; 2:105.PubMedCrossRefGoogle Scholar

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© Martinus Nijhoff Publishers, Boston 1984

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  • Gertrude Pfeiffer

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