Ammonia N 13 Injection
» Ammonia N 13 Injection is a sterile solution of 13NH3 in Sodium Chloride Injection, suitable for intravenous administration, in which a portion of the molecules are labeled with radioactive 13N (see Radiopharmaceuticals for Positron Emission Tomography—Compounding 823). It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of 13N expressed in MBq (or mCi) per mL at the time indicated in the labeling.
Specific activity: no carrier added.
Packaging and storage— Preserve in single-dose or multiple-dose containers that are adequately shielded.
Labeling— Label it to include the following, in addition to the information specified for Labeling under Injections 1: the time and date of calibration; the amount of 13N as ammonia expressed as total MBq (mCi) per mL, at time of calibration; the expiration time and 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 13N is 9.96 minutes. The label also includes the statement “Do not use if cloudy or if it contains particulate matter.”
A: Radionuclidic identity—Its half-life, determined using a suitable detector system (see Radioactivity 821 is between 9.5 and 10.5 minutes.
B: Radiochemical identity—The retention time of the major peak in the chromatogram of the Test solution corresponds to that in the chromatogram of the Standard solution, as obtained in the Radiochemical purity test.
Bacterial endotoxins 85 (see Sterilization and Sterility Assurance under Radiopharmaceuticals for Positron Emission Tomography—Compounding 823)— It contains not more than 175/V USP Endotoxin Unit per mL of the Injection, in which V is the maximum administered total dose, in mL, at the expiration time.
pH 791: between 4.5 and 7.5.
Radiochemical purity—
Mobile phase— Add 0.25 mL of concentrated nitric acid to 1000 mL of a mixture of water and methanol (7:3), filter, and degas.
Standard solution— Dissolve an accurately weighed quantity of USP Ammonium Chloride RS in water, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 0.1 mg per mL.
Test solution— Use the Injection.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 4.1-mm × 25-cm column that contains 10-µm packing L17. It is equipped with a gamma ray detector and a conductivity detector. The flow rate is about 2.0 mL per minute. Chromatograph the Test solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 5%.
Procedure— Prepare a mixture of the Standard solution and the Test solution (1:1), and inject about 20 µL of the mixture into the chromatograph, record the chromatograms, and measure the peak areas. The areas of both the main radioactive and nonradioactive peaks are equal. [note—The volume of Injection may be adjusted to obtain suitable detection system sensitivity.] The radioactivity of the major peak is not less than 95% of the total radioactivity measured. The retention time of the Test solution corresponds to the retention time of the Standard solution.
Radionuclidic purity— Using a suitable gamma-ray spectrometer (see Selection of a Counting Assembly under Radioactivity 821), count an appropriate aliquot of the Injection for a period of time sufficient to obtain a gamma spectrum. The resultant gamma spectrum should be analyzed for the presence of identifiable photopeaks which are not characteristic of 13N emissions. Not less than 99.5% of the observed gamma emissions should correspond to the 0.511 MeV, 1.022 MeV, or Compton scatter peaks of 13N.
Chemical purity— This article may be synthesized by different methods and processes and, therefore, contains different impurities. The presence of unlabeled ingredients, reagents, and by-products specific to the process must be controlled, and their potential for physiological or pharmacological effects must be considered.
aluminum (to be determined if Devarda's alloy is used to reduce 13N nitrate/nitrite)—
Aluminum standard solution— Transfer 35.17 mg of aluminum potassium sulfate dodecahydrate, accurately weighed, to a 1000-mL volumetric flask, and dilute with water to volume to obtain a solution having a known concentration of 2 µg of aluminum per mL.
Procedure— Pipet 10 mL of Aluminum standard solution into each of two 50-mL volumetric flasks. To each flask add 3 drops of methyl orange TS and 2 drops of 6 N ammonium hydroxide, then add 0.5 N hydrochloric acid, dropwise, until the solution turns red. To one flask add 25 mL of sodium thioglycolate TS, and to the other flask add 1 mL of edetate disodium TS. To each flask add 5 mL of eriochrome cyanine TS and 5 mL of acetate buffer TS, and add water to volume. Immediately determine the absorbance of the solution containing sodium thioglycolate TS at the wavelength of maximum absorbance at about 535 nm, with a suitable spectrophotometer, using the solution containing the edetate disodium TS as a blank. Repeat the procedure using two 1.0-mL aliquots of Injection. Calculate the quantity, in µg per mL, of aluminum in the Injection taken by the formula:
20(TU / TS)
in which TU and TS are the absorbances of the solutions from the Injection and the Aluminum standard solution, respectively. The concentration of aluminum ion in the Injection is not greater than 10 µg per mL.
Other requirements— It meets the requirements under Injections 1, except that the Injection may be distributed or dispensed prior to completion of the test for Sterility 71, the latter test being started within 24 hours of final manufacture, and except that it is not subject to the recommendation in Volume in Container.
Assay for radioactivity— Using a suitable calibrated system as directed under Radioactivity 821, determine the radioactivity, in MBq (or mCi) per mL, of the Injection.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Ian DeVeau, Ph.D.
Director, Veterinary Drugs and Radiopharmaceuticals
(RMI05) Radiopharmaceuticals and Medical Imaging Agents 05
Reference Standards Lili Wang, Technical Services Scientist
85 Radhakrishna S Tirumalai, Ph.D.
Senior Scientist
(MSA05) Microbiology and Sterility Assurance
USP32–NF27 Page 3095
Pharmacopeial Forum: Volume No. 29(3) Page 641
Chromatographic Column—
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.