A: Ultraviolet Absorption 197U—

B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

Buffer solution, Mobile phase, and Diluent— Proceed as directed for Test 1 in the Chromatographic purity test under Gadoteridol.

Standard solution— Prepare a solution of gadolinium (Gd III) acetate in water to obtain a solution having a known concentration of about 0.4 mg of gadolinium acetate per mL. Transfer 1.0 mL of the solution to a 10-mL volumetric flask, dilute with Diluent to volume, and mix. Transfer 1.0 mL of this solution to a small vial, add 3.0 mL of Diluent, and mix.

Test solution— Transfer an accurately measured volume of Injection, equivalent to about 150 mg of gadoteridol, to a small vial, dilute with Diluent to 5.0 mL, and mix. Immediately place in a bath maintained at about 5.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a fluorometric detector operating at an excitation wavelength of 275 nm and an emission wavelength of 314 nm and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 5.0%.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms for about 1.5 times the retention time of the gadoteridol peak, and measure the peak responses. Calculate the percentage, by weight, of free gadolinium (III) in the volume of Injection taken by the formula: in which 157.25 and 334.38 are the molecular weights of gadolinium and gadolinium acetate, respectively; C is the concentration, in mg per mL, of gadolinium (Gd III) acetate, calculated on the anhydrous basis, in the Standard solution; V is the volume, in mL, of Injection taken for the Test solution; P is the labeled potency of gadoteridol, in mg per mL, in the Injection; and rU and rS are the peak responses for free gadolinium (III) obtained from the Test solution and the Standard solution, respectively: not more than 0.02% is found.

Buffer solution, Mobile phase, Cupric acetate solution, Standard stock solution, Standard solution, and Chromatographic system— Proceed as directed for the Limit of gadoteridol related compound A test under Gadoteridol.

Test solution— Transfer an accurately measured volume of Injection, equivalent to about 30 mg of gadoteridol, to a test tube, dilute with chilled Buffer solution to 1.0 mL, and mix. Add 1.0 mL of chilled Cupric acetate solution, mix on a vortex mixer for about 10 seconds, and immediately inject as directed for Procedure.

Procedure— Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of gadoteridol related compound A in the Injection by the formula: in which C is the concentration, in µg per mL, of USP Gadoteridol Related Compound A RS in the Standard solution; V is the volume, in mL, of Injection taken for the Test solution; P is the labeled potency, in mg per mL, of gadoteridol in the Injection; and rU and rS are the peak responses of gadoteridol related compound A in the Test solution and the Standard solution, respectively: not more than 0.02% is found.

Buffer solution, Mobile phase, Standard preparation, and Chromatographic system— Proceed as directed in the Assay under Gadoteridol.

Assay preparation— Transfer an accurately measured volume of Injection, equivalent to about 150 mg of gadoteridol, to a 250-mL volumetric flask, dilute with Buffer solution to volume, and mix.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg per mL, of gadoteridol (C17H29GdN4O7) in the volume of Injection taken by the formula: in which C is the concentration, in mg per mL, of USP Gadoteridol RS in the Standard preparation; V is the volume of Injection taken, in mL; and rU and rS are the gadoteridol peak responses obtained from the Assay preparation and the Standard preparation, respectively.