» Gadoversetamide Injection is a sterile solution of Gadoversetamide in Water for Injection. It contains not less than 95.0 percent and not more than 105.0 percent of the labeled amount of gadoversetamide (C20H34GdN5O10). It may contain buffers and stabilizers. It contains no antimicrobial agents.
Packaging and storage Preserve in single-dose Type I glass containers or plastic syringes. Store at controlled room temperature.
USP Reference standards 11
USP Endotoxin RS
USP Gadoversetamide Related Compound A RS
Hydrogen [8, 11,14-tris(carboxymethyl)-6-oxo-2-oxa-5,8,11,14-tetraazahexadecan-16-oato(4-)]gadolinium.
Bacterial endotoxins 85: not more than 5 USP Endotoxin Units per mL of gadoversetamide.
pH 791: between 5.5 and 7.5.
Particulate matter 788: meets the requirements for small-volume injections.
Standard solutions Dissolve an accurately weighed quantity of manganese (II) chloride tetrahydrate in water, and quantitatively dilute with water to obtain solutions having known concentrations of 0.9 mM, 2.7 mM, and 4.5 mM.
Test stock solution Transfer 5.0 mL of the Injection to a 50-mL volumetric flask, dilute with water to volume, and mix.
Test solutions Transfer 1.0, 2.0, 4.0, and 6.0 mL of Test stock solution to individual 100-mL volumetric flasks, dilute each with water to volume, and mix. These solutions have concentrations of 0.504 mM, 1.008 mM, 2.016 mM, and 3.024 mM, respectively, based on the label claim.
Apparatus Use a mini-NMR spectrometer with suitable sensitivity (see Apparatus under Nuclear Magnetic Resonance 761).
System suitability Place a portion of each of the Standard solutions into a separate 10-mm specimen tube. Warm to 40 for not less than 10 minutes, and measure the resonance frequency (T1), at 20 MHz. The average T1 for replicate measurements must be within 5% of 156 ms for the 0.9 mM Standard solution, 52 ms for the 2.7 mM Standard solution, and 32 ms for the 4.5 mM Standard solution.
Procedure Place an accurately measured portion of each Test solution into a 10-mm specimen tube. Warm to 40 for not less than 10 minutes, and measure the resonance frequency (T1) of each Test solution. Plot 1/T1 versus the molarities of the Test solutions, and perform a regression analysis. The slope of the plotted line is the relaxivity. The relaxivity is between 4.0 and 5.0 sec1 mM1.
Solution A Proceed as directed for Mobile phase in the test for Related compounds under Gadoversetamide.
Solution B Prepare a filtered and degassed mixture of Solution A and acetonitrile (475:25).
Mobile phase Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solutions Prepare aqueous solutions of USP Gadoversetamide Related Compound A RS having known concentrations of about 30 µg per mL, 150 µg per mL, and 360 µg per mL.
Test solution Transfer 5.0 mL of the Injection to a 50-mL volumetric flask, dilute with water to volume, and mix.
Chromatographic system (see Chromatography 621) Proceed as directed in the test for Related compounds under Gadoversetamide. The chromatograph is programmed as follows.
Procedure Separately inject equal volumes (about 50 µL) of the Test Solution, the Standard solutions, and water (blank) into the chromatograph, record the chromatograms, and measure the peak responses. Allow about 1 hour between injections to remove slow-eluting impurities from the column. Calculate the percentage of gadoversetamide related compound A relative to the amount of gadoversetamide (C20H34GdN5O10) in the portion of Injection taken, based on the label claim, by the formula:
0.003Cin which C is the concentration of gadoversetamide related compound A in the Test solution, in µg per mL, obtained from the Standard response line: not more than 1.0% (w/w) of gadoversetamide related compound A is found.
Other requirements It meets the requirements of the Identification tests under Gadoversetamide. It also meets the requirements under Injections 1.
Mobile phase, Standard preparations, and Chromatographic system Proceed as directed in the Assay under Gadoversetamide.
Assay preparation Transfer about 3.0 mL of the Injection, accurately measured, to a 1000-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Procedure Proceed as directed in the Assay under Gadoversetamide. Calculate the quantity, in mg per mL, of gadoversetamide (C20H34GdN5O10) in the volume of Injection taken by the formula:
1000C/Vin which C is the concentration, in mg per mL, of gadoversetamide in the Assay preparation, obtained from the Standard response line; and V is the volume, in mL, of Injection taken.
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USP35NF30 Page 3310Pharmacopeial Forum: Volume No. 29(2) Page 415