Cyanocobalamin Co 58 Capsules

Vitamin B12- 58Co
» Cyanocobalamin Co 58 Capsules contain Cyanocobalamin in which a portion of the molecules contain radioactive cobalt (58Co) in the molecular structure. Each Capsule contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of 58Co as cyanocobalamin expressed in megabecquerels (or microcuries) at the time indicated in the labeling. The cyanocobalamin content is not less than 90.0 percent and not more than 110.0 percent of the labeled amount.
Specific activity: not less than 0.02 MBq (or 0.5 µCi) per µg of cyanocobalamin.
Packaging and storage— Preserve in well-closed, light-resistant containers, and store in a cold place.
Labeling— Label it to include the following: the date of calibration; the amount of cyanocobalamin expressed in µg per Capsule; the amount of 58Co as cyanocobalamin expressed in MBq (or µCi) per Capsule at the time of calibration; the expiration date; and the statement “Caution—Radioactive Material.” The labeling indicates that in making dosage calculations, correction is to be made for radioactive decay, and also indicates that the radioactive half-life of 58Co is 70.9 days.
USP Reference standards 11
USP Cyanocobalamin RS Click to View Structure
Disintegration 701: 30 minutes, testing one Capsule in 1 N hydrochloric acid maintained at 37 ± 2º as the immersion fluid.
Radionuclide identification 821
A: Its gamma-ray spectrum is identical to that of a specimen of 58Co that exhibits major photopeaks at 0.511 MeV (annihilation radiation) and 0.811 MeV.
B: The retention time of the major peak in the radiochromatogram of the Test solution corresponds to that in the chromatogram of the Standard solution, as obtained in the test for Radiochemical purity.
Uniformity of dosage units 905: meet the requirements.
Procedure for content uniformity— Determine the instrument response of each of 10 Capsules by measurement in a suitable counting assembly and under identical geometric conditions. Calculate the average radioactivity per Capsule. The radioactivities of none of the Capsules differ by more than 10% from the average. The relative standard deviation is less than 3.5%.
Radiochemical purity—
Mobile phase— Prepare a solution of 10.0 g of dibasic sodium phosphate in 1000 mL of water, and adjust with phosphoric acid to a pH of 3.5. Prepare a mixture of the solution so obtained and methanol (73.5:26.5), mix, and degas. Use within 2 days. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution— Transfer about 10 mg of USP Cyanocobalamin RS, accurately weighed, to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix. Transfer 2.0 mL of the solution so obtained to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Test solution— Dissolve the contents of one Capsule in 1 mL of water, allow to stand for about 10 minutes, and centrifuge. Use the supernatant.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 361-nm detector, a gamma detector adjusted for 58Co, and a 4.6-mm × 25-cm stainless steel column that contains 5-µm packing L7. The flow rate is about 1 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure.
Procedure— Inject about 100 µL of the Standard solution into the chromatograph, record the chromatogram for 30 minutes, and note the retention time of the cyanocobalamin peak. Inject 100 µL of the Test solution into the chromatograph, record the chromatogram for three times the retention time of cyanocobalamin, and measure the peak areas using the gamma detector. Calculate the percentage of cyanocobalamin present as cyanocobalamin 58Co in the portion of Capsules taken by the formula:
100(rU / rs)
in which rU is the peak area for cyanocobalamin 58Co obtained from the Test solution; and rs is the sum of all the peak areas in the radiochromatogram obtained from the Test solution: not less than 90% of the total radioactivity is found as cyanocobalamin 58Co.
Radionuclidic purity— Using a suitable, calibrated instrument (see Radioactivity 821) and standardized solutions of 58Co, 57Co, and 60Co, record the gamma spectrum. The spectrum does not differ significantly from that of the standardized 58Co solution. Determine the relative amounts of 58Co, 57Co, and 60Co present. Cobalt 57 has a half-life of 270.9 days, and its presence is shown by 0.122 MeV gamma photons. Cobalt 60 has a half-life of 5.27 years and its presence is shown by 1.173 MeV and 1.333 MeV gamma photons. Not more than 1% of the total radioactivity is due to 60Co; and not more than 2% of the total radioactivity is due to 57Co, 60Co, and other radionuclidic impurities.
Content of cyanocobalamin— Determine the content, in µg per Capsule, of cyanocobalamin as directed under Vitamin B12 Activity Assay 171.
Assay for radioactivity 821 Using a suitable counting assembly (see Selection of a Counting Assembly) and calibrated system, determine the radioactivity, in MBq (or µCi) per Capsule, of Cyanocobalamin Co 58 Capsules.
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Topic/Question Contact Expert Committee
Monograph Ravi Ravichandran, Ph.D.
Principal Scientific Liaison
(SM42010) Monographs - Small Molecules 4
Reference Standards RS Technical Services
701 Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison
(GCDF2010) General Chapters - Dosage Forms
USP35–NF30 Page 2752
Pharmacopeial Forum: Volume No. 27(6) Page 3395