Flumazenil C11Injection
»Flumazenil C11Injection is a sterile solution,suitable for intravenous administration,of Flumazenil in which a portion of the molecules are labeled at the N-position with radioactive 11C.It contains not less than 90.0percent and not more than 110percent of the labeled amount of 11Cexpressed in MBq (or mCi)at the time indicated in the labeling.Its specific activity is not less than 14.8GBq (400mCi)per µmol.It may contain suitable buffers.
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 11Cas [N-methyl-11C]Flumazenil,expressed as MBq (or mCi);the specific activity,expressed as MBq (or mCi)per µmol;the concentration,expressed as MBq (or mCi)per mL,at the date and time of calibration;the expiration date and time;the lot or batch number;the name and quantity of any added preservative or stabilizer;and the statements,“Caution—Radioactive Material”and “Do not use if cloudy or if it contains particulate matter.”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 20minutes.
Radionuclide identification 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 mL,in which Vis the maximum recommended total dose,in mL,at the expiration date or time.
pHá791ñ: between 4.5and 8.5.
Radionuclidic purity á821ñ— Using a multichannel analyzer,count all radioactivity from 40to 2,500keVto determine the absence of radiation,other than at 0.511MeVand 1.022MeV,over a period of 4hours.Determine the half-life (20minutes)by a suitable detector system.
Chemical purity—
Mobile phase— Transfer 1.2g of monobasic sodium phosphate to a 1000-mLvolumetric flask,dissolve in 500mLof deionized distilled water,and dilute with deionized distilled water to volume to obtain a stock solution.Transfer 300mLof acetonitrile to another 1000-mLvolumetric flask,and dilute with the stock solution to volume.Filter and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
System suitability solution— Dissolve an accurately weighed quantity of USP Flumazenil RSin acetonitrile to obtain a solution having a known concentration of 1mg of flumazenil per mL.Dilute a portion of this solution quantitatively with Mobile phaseto obtain a solution having a known concentration of about 10µg of flumazenil per mL.
Test solution— Pipet an accurately measured volume of Injection into a suitable container,and dilute with Mobile phaseto obtain a solution containing about 0.1mLof flumazenil per mL.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×25-cm column that contains packing L1.The flow rate is about 2mLper minute.The column temperature is maintained at 20.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the column efficiency is not less than 100theoretical plates;the tailing factor is not more than 1.1;and the relative standard deviation for replicate injections is not more than 3.2%.
Procedure— Inject about 20µLof the Test solutioninto the chromatograph,record the chromatogram,and measure the peak responses.Separately calculate the percentage of each impurity in the portion of the Injection taken by the formula:
100(ri/rs),
in which riis the peak response for each impurity;and rsis the sum of the responses of all the peaks:not more than 0.2%of any individual impurity is found,and not more than 0.9%of total impurities is found.
Radiochemical purity á821ñ—
Mobile phase and System suitability solution—Prepare as directed in the test for Chemical purity.
Chromatographic system— Proceed as directed in the test for Chemical purity,except that the liquid chromatograph is also equipped with a suitable collimated radiation detector (see Radioactivity á821ñ).
Procedure— Inject about 20µLof the Injection into the chromatograph,record the chromatogram,and measure responses for the major peaks.The radioactivity under the main peak is not less than 98%of the total radioactivity measured.
Specific activity—
Mobile phase and System suitability solution—Proceed as directed in the test for Chemical purity.
Chromatographic system— Proceed as directed in the test for Chemical purity,except that the liquid chromatograph is also equipped with a suitable collimated radiation detector (see Radioactivity á821ñ).
Procedure— Calculate the specific activity,in MBq (or mCi)per µmol,of Injection by the formula:
3.03(CRPR)/C,
in which CRis the radioactivity content,in MBq (or mCi)per mL,as determined in the Assay for radioactivity;PRis the radiochemical purity (in %),as determined in the test for Radiochemical purity;and Cis the concentration,in µg per mL,of flumazenil in the Injection as determined in the test for Chemical purity.The specific activity is not less than 400mCi per µmol.
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 on the day following final manufacture,and except that it is not subject to the recommendation on Volume in Container.
Assay for radioactivity á821ñ— Using a suitable counting assembly (see Selection of a Counting Assembly),determine the radioactivity,in MBq (or mCi)per mL,of 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 350
Phone Number:1-301-816-8305