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
Labeling under
Injections 
1
: the time and date of calibration; the amount of
11C as [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
11C is 20 minutes.
Radionuclide identification 821—
Its gamma-ray spectrum is identical to that of a specimen of
11C in that it exhibits a positron annihilation peak at 0.511 MeV and possibly a sum peak of 1.022 MeV, dependent upon geometry and detector efficiency.
Bacterial endotoxins 85—
It contains not more than 175/
V USP Endotoxin Unit per mL, in which
V is the maximum recommended total dose, in mL, at the expiration date or time.
Radionuclidic purity 821—
Using a multichannel analyzer, count all radioactivity from 40 to 2,500 keV to determine the absence of radiation, other than at 0.511 MeV and 1.022 MeV, over a period of 4 hours. Determine the half-life (20 minutes) by a suitable detector system.
Chemical purity—
Mobile phase—
Transfer 1.2 g of monobasic sodium phosphate to a 1000-mL volumetric flask, dissolve in 500 mL of deionized distilled water, and dilute with deionized distilled water to volume to obtain a stock solution. Transfer 300 mL of acetonitrile to another 1000-mL volumetric flask, and dilute with the stock solution to volume. Filter and degas. Make adjustments if necessary (see
System Suitability under
Chromatography 621).
System suitability solution—
Dissolve an accurately weighed quantity of
USP Flumazenil RS in acetonitrile to obtain a solution having a known concentration of 1 mg of flumazenil per mL. Dilute a portion of this solution quantitatively with
Mobile phase to obtain a solution having a known concentration of about 10 µg of flumazenil per mL.
Test solution—
Pipet an accurately measured volume of Injection into a suitable container, and dilute with Mobile phase to obtain a solution containing about 0.1 mL of flumazenil per mL.
Chromatographic system
(see
Chromatography 621)—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 2 mL per 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 100 theoretical 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 20 µL of the
Test solution into 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
ri is the peak response for each impurity; and
rs is 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 821—
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 821).
Procedure—
Inject about 20 µL of 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 821).
Procedure—
Calculate the specific activity, in MBq (or mCi) per µmol, of Injection by the formula:
3.03(CRPR) / C,
in which
CR is the radioactivity content, in MBq (or mCi) per mL, as determined in the
Assay for radioactivity; PR is the radiochemical purity (in %), as determined in the test for
Radiochemical purity; and
C is 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 400 mCi per µmol.
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 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 821—
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.
