National Institute of C&D for Physics and Nuclear Engineering (IFIN-HH) “Horia Hulubei”

1. National Institute of C&D for Physics and Nuclear Engineering (IFIN-HH) “Horia Hulubei” “Gamma Spectrometry and Neutron Activation Analysis used in Pharmaceutical products quality control”

2. IFIN-HH

3. CPR DEPARTMENT RESEARCH -PRODUCTION RADIOISOTOPES AND RADIOPHARMACEUTICAL PRODUCTS CENTRE ANALYSIS LABORATORY

4. ANAYSIS LABORATORY Since 2001 • CERTIFICATE LABORATORY of National Commission for Nuclear Activities Control (CNCAN)

7. Domains of tests • 1.Qualitative and Quantitative Physico-chemical Analysis: • Atomic Absorbtion Spectrofotometry; • UV-Vis Spectrofotometry; • Neutron Activation Analysis; • Gravimetrical and volumetrical methods; • pH determinations; • 2.Radionuclidic analysis –Gamma spectrometry; • 3.Radiochemical analysis-radiocromatographyque method; • 4.Microbiological analysis (sterility; pirogenity; toxicity; biodistribution determinations); • 5.Activity measurements ; • 6.Dosimetrycal measurements • 7.Examination of Radioactive sources

8. Gamma Spectrometry it’s using in our Laboratory for: • Radiopharmaceutical Quality Control; • Radionuclidic purity determination; • Activity measurement; • Radionuclides identification; • Radioactive contamination control; • Neutron Activation Analysis

9. Gamma Spectrometry • CANBERRA Equipment consist in: • HP Ge detector with preamplificator; • Tension source with (0-4000) V domain; • ACCUSPEC-A multi-channel analyzer; • PC with analysis program • The detector was calibrated in energy ( 50-1500 keV) domain, using a standards set.

10. Radionuclidic purity determination For principales Radiopharmaceuticals producted in our Department: • Na131I solution used in thyroidian cancer radiotheraphy; • Gelatine capsules with Na131I used in thyroidian affections diagnosis; • 99Mo-99mTc ROMTEC Generator for diagnosis P RN is calculated as proportion between the activity of specific radionuclide and the sum of all determined radionuclides activities PRN for radiopharmaceutical products must be more 99.9%

14. Neutron Activation Analysis is used in our Laboratory for: • To determine possible impurities from not radioactive raw materials; • To determine the content of microelements in new pharmaceutical products

16. Target for neutron activation Closed by welding h = 100 mm Lead  25 mm Sample Target for neutron activation height = 100 mm Aluminium capsule Sample and standards Lead  25 mm

17. Element Radioisotopes results from (n,) reaction Half time Gamma ray (keV) Scheme factor Na 24Na 15.03 h 1368 100 Mg 27Mg 9.47 min. 1014 28 Al 28Al 2.31 min. 1778 100 Cl 38Cl 37.3 min. 1642 32.8 K 42K 12.36 h 1525 17.8 Ca 47Ca 3.4 d 159 70 Sc 46Sc 83.9 d 889 100 V 52V 3.75 min. 1434 100 Mn 56Mn 2.58 h 847 99 Fe 59Fe 44.6 d 1099 56 Co 60Co 5.27 y 1173 100 La 140La 40.3 h 1596 96

18. Element Unit of concentration  Leaf Stem Root Uncertainty (%) Na ppm 150 90 6750 5 Mg ppm 800 940 1370 25 Al ppm 320 680 2420 25 Cl ppm 1320 3490 2520 10 K % 3.34 4.91 1.46 2 Ca % 5.56 - 0,21 2 Sc ppm - - 1 30 V ppm 1 - 11 50 Mn ppm 45 20 45 5 Fe % 0.08 - - 10 Co ppm 0.5 1.5 2 10 La ppm 0.2 - 0.6 15 • Big variations of concentrations from element to element (from ppm to %) and differences of content for each element on different segments of plant

19. Conclusion: • Gamma Spectrometry and Neutron Activation Analysis are two very sensitive methods for pharmaceutical quality control