Ammonia N13Injection
»Ammonia N13Injection is a sterile solution of 13NH3in 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 á823ñ).It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of 13Nexpressed in MBq (or mCi)per mLat 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 Labelingunder Injections á1ñ:the time and date of calibration;the amount of 13Nas 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 13Nis 9.96minutes.The label also includes the statement “Do not use if cloudy or if it contains particulate matter.”
Identification—
A: Radionuclidic identity—Its half-life,determined using a suitable detector system (see Radioactivity á821ñis between 9.5and 10.5minutes.
B: Radiochemical identity—The retention time of the major peak in the chromatogram of the Test solutioncorresponds to that in the chromatogram of the Standard solution,as obtained in the Radiochemical puritytest.
Bacterial endotoxins á85ñ(seeSterilization and Sterility Assurance under Radiopharmaceuticals for Positron Emission Tomography—Compounding á823ñ)— It contains not more than 175/VUSP Endotoxin Unit per mLof the Injection,in which Vis the maximum administered total dose,in mL,at the expiration time.
pHá791ñ: between 4.5and 7.5.
Radiochemical purity—
Mobile phase— Add 0.25mLof concentrated nitric acid to 1000mLof a mixture of water and methanol (7:3),filter,and degas.
Standard solution— Dissolve an accurately weighed quantity of USP Ammonium Chloride RSin water,and dilute quantitatively,and stepwise if necessary,with water to obtain a solution having a known concentration of about 0.1mg per mL.
Test solution— Use the Injection.
Chromatographic system(see Chromatography á621ñ)— 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 2.0mLper 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 solutionand the Test solution(1:1),and inject about 20µLof 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 solutioncorresponds to the retention time of the Standard solution.
Radionuclidic purity— Using a suitable gamma-ray spectrometer (see Selection of a Counting Assemblyunder Radioactivity á821ñ),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 13Nemissions.Not less than 99.5%of the observed gamma emissions should correspond to the 0.511MeV,1.022MeV,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 13Nnitrate/nitrite)—
Aluminum standard solution— Transfer 35.17mg of aluminum potassium sulfate dodecahydrate,accurately weighed,to a 1000-mLvolumetric flask,and dilute with water to volume to obtain a solution having a known concentration of 2µg of aluminum per mL.
Procedure— Pipet 10mLof Aluminum standard solutioninto each of two 50-mLvolumetric flasks.To each flask add 3drops of methyl orange TSand 2drops of 6Nammonium hydroxide,then add 0.5Nhydrochloric acid,dropwise,until the solution turns red.To one flask add 25mLof sodium thioglycolate TS,and to the other flask add 1mLof edetate disodium TS.To each flask add 5mLof eriochrome cyanine TSand 5mLof acetate buffer TS,and add water to volume.Immediately determine the absorbance of the solution containing sodium thioglycolate TSat the wavelength of maximum absorbance at about 535nm,with a suitable spectrophotometer,using the solution containing the edetate disodium TSas a blank.Repeat the procedure using two 1.0-mLaliquots of Injection.Calculate the quantity,in µg per mL,of aluminum in the Injection taken by the formula:
20(TU/TS),
in which TUand TSare 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 10µg per mL.
Other requirements— It meets the requirements under Injections á1ñ,except that the Injection may be distributed or dispensed prior to completion of the test for Sterility á71ñ,the latter test being started within 24hours 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 á821ñ,determine the radioactivity,in MBq (or mCi)per mL,of the Injection.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 1384
Pharmacopeial Forum:Volume No.29(3)Page 641
Phone Number:1-301-816-8305