USP Guideline For

SODIUM ACETATE ([1-11C]) detector operating in the range of 190 to 290 nm in series. INJECTION Mobile phase: 95.5 % 400 mM K2HPO4 and of 0.5% acetonitrile (v:v). 11 CH3[ C] O2 Na Column: 4.6-mm × 150-mm column that contains packing L21 (spherical styrene divinyl Sodium [1-11C ] Acetate copolymer) or similar column. DEFINITION Flow rate: ~ 0.75 mL per min. Sodium [1-11C ] Acetate injection is a sterile solution, Injection volume: 20 μL suitable for intravenous administration, of Sodium System suitability (UV Detector) Acetate in which a portion of the carbonyl molecules Sample: Standard solution are labeled with radioactive 11C (see Suitability requirements Radiopharmaceuticals for Positron Emission Column efficiency: NLT 2,000 theoretical Tomography – Compounding <823>). It contains plates NLT 90% and NMT 110% of the labeled amount of Tailing factor: NMT 2.0 11C expressed in MBq (or mCi) at the time indicated % RSD: 2% in the labeling. It may contain suitable buffers. Suitability (Gamma-ray Detector) Samples: Use the injection diluted in IDENTIFICATION mobile phase Suitability requirements  ADIONUCLIDIC DENTITY R I Column efficiency: NLT 2,000 theoretical Analysis: The T½ of 20.4 minutes is determined plates using a suitable detector system. The data Tailing factor: NMT 2.0 should be recorded over an appropriate time and % RSD: 5% used to calculate the half-life. Analysis: Prepare a mixture of the Test solution Acceptance criteria: The T½ is NLT 19.9 min and the Standard solution as described in and NMT 20.9. radiochemical identification, inject into the  RADIOCHEMICAL IDENTIFICATION chromatograph, record the chromatograms, and Analysis: Obtain a chromatogram as measure the areas for the radioactive peaks. The described in Radiochemical purity. The ratio and injected volume may be adjusted to retention time of the major peak in the obtain suitable detection system sensitivity. chromatogram of the Test solution corresponds Determine the radiochemical purity by dividing to that in the chromatogram of the Standard the area of the [11C]acetate radioactivity peak solution, as obtained in the test for (see test for radiochemical identity) by sum of all Radiochemical purity. radioactivity peak areas. Acceptance criteria: The retention times of the Acceptance criteria: The radiochemical purity is 11 sodium acetate and [ C]acetate fall within ± 10% NLT 90%. of each other. [NOTE—the typical retention time for [11C]acetate is about 2.9 min and for sodium  RADIONUCLIDIC PURITY acetate about 2.8 min.] Analysis: Count an appropriate aliquot of injection for a period of time sufficient to obtain a ASSAY gamma spectrum. The resultant gamma  RADIOACTIVITY <821> spectrum should be analyzed for the presence of Analysis: Using a suitable calibrated system identifiable photopeaks which are not (see Radioactivity <821>), determine the characteristic of 11C emissions. radioactivity of the Sample solution, in MBq (or Acceptance criteria: Carbon-11: minimum 99.5 mCi) per mL, of the Injection. percent of the total radioactivity of the gamma emissions should correspond to the 0.511 MeV PURITIES (annihilation peak), 1.022 MeV (sum peak), or 11  RADIOCHEMICAL PURITY Compton scatter peaks of C, with no individual Standard solution: 20 mg/mL of sodium impurity peaks present above 0.5 % at time of acetate RS in mobile phase. injection determined using a suitable gamma-ray Sample solution: Use the Injection diluted in spectrometer (see Selection of a Counting mobile phase. Assembly under Radioactivity <821>. Liquid Chromatographic system Mode: HPLC  CHEMICAL PURITY Detectors: Flow through radioactivity The methods and limits described in this section detector, and a variable wavelength UV relate to potential impurities associated with commonly used methods of synthesis. If other

1 methods of synthesis result in impurities with ADDITIONAL REQUIREMENTS toxic potential, they must be determined to be  PACKAGING AND STORAGE: Preserve in single- within acceptable limits, and conformance with dose or multiple-dose containers that are these limits demonstrated by the use of one or adequately shielded. more validated limit tests. Sodium acetate:  USP REFERENCE STANDARDS <11>: If the particular production method is incapable of USP Endotoxin RS producing an amount of acetate in excess of 2.0 % (w/100 mL) then measurement of the acetate USP sodium acetate RS quantity is not required. Standard solution: sodium acetate RS 20 mg/V in mobile phase, V being the maximum recommended dose in milliters. Sample solution: Use the Injection diluted in mobile phase. Analysis: Obtain chromatograms as directed in the test for Radiochemical purity. On the UV chromatogram for the Standard solution, measure the peak area for the peak associated with sodium acetate RS. Measure the peak area for the corresponding peak in the UV chromatogram for the Sample solution. Acceptance Criteria: Not more than the area of the corresponding peak in the chromatogram obtained with the reference solution (20 mg per V) Residual Solvents are limited according to General Chapter <467> Residual Solvents

SPECIFIC TESTS  BACTERIAL ENDOTOXINS <85>: The final product cannot contain more than 175 USP Endotoxin Units in the entire batch volume of sodium [11C]acetate Injection.  PH Sample solution: Use the Injection. Analysis: Apply the Sample solution to pH paper strips that have a resolution of at least 1 pH unit. Observe and record the results immediately after the color changes are complete. Acceptance criteria: 4.0 – 9.0  FILTER INTEGRITY: Use the bubble point measurement to test the membrane filter integrity. The acceptance criteria for the bubble point should be in accordance with the filter manufacturer’s specification(s).  OTHER REQUIREMENTS: The final product meets the requirements under Injections <1>, except that the Injection may be distributed or dispensed prior to completion of the test for Sterility <7> and it is not subject to the recommendation in Volume in Container (see Radiopharmaceuticals for Positron Tomography-Compounding <823>). The Sterility test should be started within 30 hours of end of synthesis.