Packaging and storage— Preserve in a single-dose container that is 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 15Oas water expressed as MBq (mCi)per mL,at time of calibration;total activity 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 15Ois 2.03minutes.The label also includes the statement,“Do not use if cloudy or if it contains particulate matter.”

USP Reference standards á11ñ— USP Endotoxin RS.

Identification—

Bacterial endotoxins á85ñ (see Sterilization and Sterility Assuranceunder Radiopharmaceuticals for Positron Emission Tomography—Compounding á823ñ)—It contains not more than 175/VEndotoxin Unit per mLof Injection,in which Vis the maximum administered total dose,in mL,at the expiration time.

Sterility á71ñ: meets the requirements.

pHá791ñ: between 4.5and 8.0.

Radiochemical purity— The gas chromatograph (see Chromatography á621ñ)is equipped with thermal conductivity and radioactivity detectors and a 0.53-mm ×30-m column coated with a film of G16stationary phase.The column temperature is maintained at 40,and the injector and detector temperatures are maintained at 250and 200,respectively.The carrier gas is helium,flowing at a rate of about 10mLper minute.Inject about 50µLof the Injection into the chromatograph,record the chromatogram,and measure the responses for the major peaks of both the radioactive and the nonradioactive detection systems (the volume of Injection being adjusted,if necessary,to obtain suitable detection system sensitivity):the column efficiency determined from the analyte peak is not less than 10,000theoretical plates;the tailing factor for the analyte peak is not more than 1.5;and the relative standard deviation for replicate injections is not more than 5%.Not less than 95%of the radioactivity is Water O15,and the retention time of the Water O15corresponds to the retention time of the water contained within the product formulation.

Radionuclidic purity— Using a gamma-ray spectrometer (see Selection of a Counting Assembly under 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 15Oemissions.Not less than 99.5%of the observed gamma emissions should correspond to the 0.511MeV,1.022MeV,or Compton scatter peaks of 15O.

Chemical purity— This article can be synthesized by different methods and processes and,therefore,may contain 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.

Heavy metals,Method Iá231ñ: 5ppm.

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 being started within 24hours of final manufacture,and except that it is not subject to the recommendation for Volume in Container.

Assay for radioactivity— Using a suitable calibrated system as directed under Radioactivity á821ñ,determine the radioactivity of the Injection,in MBq (or mCi)per mL.

Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents

USP28–NF23Page 1443

Phone Number:1-301-816-8305