Iodohippurate Sodium I123Injection
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Glycine,N-[2-(iodo-123I)benzoyl]-,monosodium salt.
Sodium o-iodo-123I-hippurate [56254-07-0].
»Iodohippurate Sodium I123Injection is a sterile,aqueous solution containing o-iodohippurate sodium in which a portion of the molecules contain radioactive iodine (123I)in the molecular structure.It may contain a preservative or stabilizer.
Iodohippurate Sodium I123Injection contains not less than 90.0percent and not more than 110.0percent of the labeled amount of I123as iodohippurate sodium expressed in megabecquerels (microcuries or millicuries)per mLat the time indicated in the labeling.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of o-iodohippuric acid.Other chemical forms of radioactivity do not exceed 3.0percent of total radioactivity.
Packaging and storage—
Preserve in single-dose or in 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 I123as iodohippurate sodium expressed as total megabecquerels (microcuries or millicuries)per mLat the time of calibration;the name and quantity of any added preservative or stabilizer;the expiration time;and the statement “Caution—Radioactive Material.”The labeling indicates that in making dosage calculations,correction is to be made for radioactive decay,and also indicates that the radioactive half-life of I123is 13.2hours.
Radionuclidic identification (see Radioactivity á821ñ)—
Its gamma-ray spectrum is identical to that of a specimen of I123of known purity that exhibits a major photopeak having an energy of 159keV.
Bacterial endotoxins á85ñ—
The limit of endotoxin content is not more than 175/VUSP Endotoxin Unit per mLof the Injection,when compared with the USP Endotoxin RS,in which Vis the maximum recommended total dose,in mL,at the expiration time.
pHá791ñ:
between 7.0and 8.5.
Radionuclidic purity—
Using a suitable counting assembly (see Selection of a Counting Assemblyunder Radioactivity á821ñ),determine the radionuclidic purity of the Injection:not less than 85%of the total radioactivity is present as I123.
Radiochemical purity—
Mobile phase,Standard preparation,andChromatographic system—
Proceed as directed in the Assay for o-iodohippuric acid,except to provide that the liquid chromatograph is also equipped with a radioactivity detector (see Radioactivity á821ñ).
Procedure—
Inject about 50µLequivalent to 1.8to 3.7MBq (50to 100µCi)of Injection into the chromatograph,record the chromatogram,and measure the area of all radioactivity peaks.The radioactivity under the o-iodohippuric acid I123peak is not less than 97.0%of the total area of all peaks observed,and its retention time is within ±10%of the value obtained for USPo-Iodohippuric Acid RS.
Biological distribution—
Inject intravenously between 0.75and 22MBq (20and 600µCi)of the Injection,in a volume of 0.10mLto 0.15mL,into the caudal vein of each of three 125-g to 225-g anesthetized rats.Clamp the opening of the urethra with a hemostat.Sacrifice the animals 1hour after administration,and carefully remove the intact bladder and contents and thyroid by dissection.Place each organ and remaining carcass (excluding the tail)in separate,suitable counting containers,and determine the radioactivity,in counts per minute,in each container with an appropriate detector using the same counting geometry.Determine the percentage of radioactivity in each organ:not less than 75%of the administered dose is found in the bladder,and not more than 3%of the administered dose is found in the thyroid in two of the rats.
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,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 o-iodohippuric acid—
Mobile phase—
Prepare a filtered and degassed mixture of water,methanol,and glacial acetic acid (75:25:1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation—
Using an accurately weighed quantity of USPo-Iodohippuric Acid RS,prepare a solution in water having a known concentration of about 2mg per mL.
Assay preparation—
Use Iodohippurate Sodium I123Injection.
Chromatographic system(see Chromatography á621ñ)—
The liquid chromatograph is equipped with a 265-nm detector and an 8-mm ×10-cm column that contains packing L11.The flow rate is about 5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed under Procedure:the column efficiency determined from the analyte peak is not less than 500theoretical plates,the tailing factor for the analyte peak is not more than 1.5,and the relative standard deviation for replicate injections is not more than 1.5%.
Procedure—
Separately inject equal volumes (about 50µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatogram,and measure the responses for the major peaks.Calculate the quantity,in mg,of o-iodohippuric acid in each mLof Injection taken by the formula:
C(rU/rS),
in which Cis the concentration,in mg per mL,of USPo-Iodohippuric Acid RSin the Standard preparation,and rUand rSare the o-iodohippuric acid peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Assay for radioactivity—
Using a suitable counting assembly (see Selection of a Counting Assemblyunder Radioactivity á821ñ),determine the radioactivity in MBq (µCi or mCi)per mLof Injection by use of a calibrated system as directed under Radioactivity á821ñ.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 1032
Phone Number:1-301-816-8305