Indium In 111Pentetreotide Injection
»Indium In 111Pentetreotide Injection is a sterile solution,suitable for intravenous administration,containing radioactive indium (111In)in the form of a chelate of pentetreotide.It contains not less than 90.0percent and not more than 110percent of the labeled amount of 111In as the pentetreotide complex expressed in megabecquerels (or in millicuries)per mLat the time indicated in the labeling.It may contain sodium chloride,stabilizers,and buffers.Other forms of radioactivity do not exceed 10.0percent of the total radioactivity.
Packaging and storage— Preserve in single-dose containers.
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 111In as labeled pentetreotide complex expressed as total megabecquerels (or millicuries)and the concentration expressed as megabecquerels (or millicuries)per mLon the date and time of calibration;the expiration date;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 111In is 67.3hours.
Radionuclide identification (see Radioactivity á821ñ)— Its gamma-ray spectrum is identical to that of a specimen of 111In that exhibits major photopeaks having energies of 0.171and 0.245MeV.
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 3.8and 4.3.
Radiochemical purity—
Solution A— Dissolve 6.8g of sodium acetate in 500mLof water.Adjust with glacial acetic acid to a pHof 5.5,dilute with water to 1000mL,and mix.Filter through a filter having a porosity of 0.5µm or less,and degas.
Solution B— Use methanol.
Mobile phase— Use variable mixtures of Solution Aand Solution Bas directed under Chromatographic system.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 3.9-mm ×30-cm stainless steel column that contains 10-µm packing L1.It is also equipped with a flow-through gamma-ray detector having a cell volume of about 50µLand calibrated to provide a linear response within the range of 0.5to 15MBq (14to 400µCi).The column temperature is maintained at 35.The chromatograph is programmed to provide variable mixtures of Solution Aand Solution B,and the initial flow rate is about 1mLper minute.The column is equilibrated for at least 15minutes with a mobile phase consisting of 60%Solution Aand 40%Solution B.After injection,the composition of the mobile phase is changed linearly to 20%Solution Aand 80%Solution Bat 20minutes,then changed to 100%Solution Bover the next 0.1minute,and is held at that percentage while the flow rate is increased linearly from 1to 2mLover the next 5minutes,which is the end of the run.Counts are recorded and charted for 25minutes at about 2-second intervals.
Procedure— Constitute the Injection,and allow to stand for 30minutes.Inject a volume of Injection having an activity of 0.5to 15MBq (14to 400µCi)into the chromatograph,and record the chromatogram.The retention time of the 111In pentetreotide peak (which should elute as a double peak)is between 4and 5relative to that of unbound 111In.Record the counts for the 111In pentetreotide,unbound 111In,other impurity peaks,and a representative baseline segment,and calculate the percentage of radioactivity from 111In pentetreotide by the formula:
100P/(P+O),
in which Pis the count of the 111In pentetreotide peak,and Ois the count for all other peaks,each being corrected for its corresponding baseline count.The radioactivity of 111In pentetreotide is not less than 90%of the total radioactivity.
Radionuclidic purity á821ñ— Using a suitable counting assembly (see Selection of a Counting Assembly),determine the radioactivity of each radionuclidic impurity,in kBq per MBq (or µCi per mCi)of 111In,in the Injection by use of a calibrated system.
INDIUM 114m—The presence of 114mIn in the Injection is demonstrated by a characteristic gamma-ray spectrum with prominent photopeaks having energies of 0.192,0.558,and 0.724MeV.114mIn decays with a radioactive half-life of 49.5days.The amount of 114mIn is not greater than 3kBq per MBq (3µCi per mCi)of 111In.
ZINC 65—The presence of 65Zn in the Injection is demonstrated by a characteristic gamma-ray spectrum with a prominent photopeak at 1.115MeV.65Zn decays with a radioactive half-life of 243.9days.The amount of 65Zn is not greater than 3kBq per MBq (3µCi per mCi)of 111In.
Other requirements— It meets the requirements under Injections á1ñ,except that the Injection may be distributed or dispensed prior to the completion of the test for Sterility á71ñ,the latter test being started on the day of 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 Assemblyunder Radioactivity á821ñ),determine the radioactivity,in MBq per mLof 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 1011
Phone Number:1-301-816-8305