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 Labeling under Injections 1: the time and date of calibration; the amount of 15O as 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 15O is 2.03 minutes. The label also includes the statement, “Do not use if cloudy or if it contains particulate matter.”

USP Reference standards 11— USP Endotoxin RS.

Identification—

Bacterial endotoxins 85 (see Sterilization and Sterility Assurance under Radiopharmaceuticals for Positron Emission Tomography—Compounding 823)—It contains not more than 175/V Endotoxin Unit per mL of Injection, in which V is the maximum administered total dose, in mL, at the expiration time.

Sterility 71: meets the requirements.

pH 791: between 4.5 and 8.0.

Radiochemical purity— The gas chromatograph (see Chromatography 621) is equipped with thermal conductivity and radioactivity detectors and a 0.53-mm × 30-m column coated with a film of G16 stationary phase. The column temperature is maintained at 40, and the injector and detector temperatures are maintained at 250 and 200, respectively. The carrier gas is helium, flowing at a rate of about 10 mL per minute. Inject about 50 µL of 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 10,000 theoretical 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 O 15, and the retention time of the Water O 15 corresponds 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 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 15O 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 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 I 231: 5 ppm.

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 being started within 24 hours 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 821, determine the radioactivity of the Injection, in MBq (or mCi) per mL.

Expert Committee : (RMI05) Radiopharmaceuticals and Medical Imaging Agents 05

USP29–NF24 Page 1611

Phone Number : 1-301-816-8305