Methionine C11Injection
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»Methionine C11Injection is a sterile isotonic solution,suitable for intravenous administration of 
L[11C]methionine,USP28in which a portion of the molecules are labeled with radioactive 11C.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of 11Cexpressed in MBq (or in mCi)at the time indicated in the labeling.It may contain preservatives and stabilizers.
L[11C]methionine,USP28in which a portion of the molecules are labeled with radioactive 11C.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of 11Cexpressed in MBq (or in mCi)at the time indicated in the labeling.It may contain preservatives and stabilizers.
Specific activity:
not less than 37.0GBq (1.0Ci)per mmol.
Packaging and storage—
Preserve in single-dose or multiple-dose containers that are adequately shielded.
Labeling—
Label it to include the following:the time and date of calibration;the amount of 11Cas methionine expressed as total MBq (or mCi)per mLat time of calibration;the expiration time and date;the name and quantity of any added preservative or stabilizer;and the statement “Caution—Radioactive Material.”The labeling indicates that in making dosage calculations,correction is to be made for radioactive decay,and states that the radioactive half-life of 11Cis 20.4minutes.Each container to hold 11Cmethionine shall be independently labeled to indicate lot number and batch number.The labeling states that a microbiological filter (0.22µm)is to be in place to remove any possible particulate matter that could be carried through to the final product.
Radionuclide identification (see Radioactivity á821ñ)—
Its gamma-ray spectrum is identical to that of a specimen of 11Cin that it exhibits a positron annihilation peak at 0.511MeVand possibly a sum peak of 1.022MeV,dependent upon geometry and detector efficiency.
Bacterial endotoxins á85ñ—
It contains not more than 175/VUSP Endotoxin Unit per mLof the Injection,in which Vis the maximum recommended total dose,in mL,at the expiration time.
pHá791ñ:
between 6.0and 8.0.
Radionuclidic purity á821ñ—
Using a suitable gamma-ray spectrometer,determine the absence of radiation other than at 0.511MeV,over a period of 20minutes.Determine the half-life (20.41minutes)by a suitable detector system.
Chemical purity—
Mobile phase—
Prepare a filtered and degassed mixture of 0.008Mcopper acetate and 0.017ML-proline.Adjust with 0.030Msodium acetate to a pHof 5.Make adjustments,if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard solution—
Dissolve an accurately weighed quantity of DL-methionine in Mobile phaseand dilute quantitatively,and stepwise if necessary,to obtain a solution containing 0.1mg per mL.
Test solution—
Pipet a volume of Injection into a suitable container,and dilute with Mobile phaseto obtain a solution containing about 0.1mg per mL.
Chromatographic system
(see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×15-cm column that contains packing L1.The flow rate is about 0.5mLper minute.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the relative retention times are 1.0for D-methionine and 2.4for L-methionine;the resolution,R,between the D-and L-enantiomers is not less than 1.5;the column efficiency is not less than 1400theoretical plates;the tailing factor is not more than 2.0;and the relative standard deviation for replicate injections is not more than 2%.
Procedure—
Inject a volume (about 10µL)of the Test solutioninto the chromatograph,record the chromatogram,and measure the peak responses.Calculate the percentage of D-methionine in the portion of Injection taken by the formula:
100(ri/rs),
in which riis the peak response for D-methionine,and rsis the sum of the responses of all of the peaks:not more than 4%of D-enantiomer is found.
Radiochemical purity—
Proceed as directed under Chemical purity.The radioactivity of the main peak is not less than 98%of the total radioactivity measured.
Other requirements—
It meets the requirements under Injections á1ñ,except that the Injection may be distributed or dispensed prior to completion of the tests for Sterility á71ñand Bacterial Endotoxins á85ñ,these tests being started on the day of final manufacture,and except that it is not subject to the recommendation of Volume in container.
Assay for radioactivity á821ñ—
Using a suitable counting assembly (see Selection of a Counting Assembly),determine the radioactivity,in GBq (Ci)per mL,of the Injection by use of a calibrated system.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 352
Pharmacopeial Forum:Volume No.30(3)Page 811
Phone Number:1-301-816-8305