Valrubicin Intravesical Solution
» Valrubicin Intravesical Solution is a sterile solution of Valrubicin in a suitable vehicle. It contains not less than 95.0 percent and not more than 105.0 percent of the labeled amount of valrubicin (C34H36F3NO13).
Packaging and storage Preserve in single-dose or multiple-dose containers, preferably of Type I glass. Store in a refrigerator.
Labeling Label it to indicate that it is not intended for intravenous or intramuscular injection, but is to be used for intravesical instillation.
USP Reference standards 11
USP Endotoxin RS.
USP Valrubicin RS .
USP Valrubicin Related Compound A RS .
A: Thin-Layer Chromatographic Identification Test 201
Test solution Use the Assay preparation, prepared as directed in the Assay, and suitably dilute with methanol.
Standard solution Use the Standard preparation, prepared as directed in the Assay, and suitably dilute with methanol.
Developing solvent system Use the Mobile phase, prepared as directed in the Assay.
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.
Bacterial endotoxins 85: not more than 0.14 USP Endotoxin Unit per mg of valrubicin.
pH 791: between 4.0 and 7.0, in a solution of 0.9% sodium chloride (1 in 15).
Mobile phase Prepare as directed in the Assay.
Resolution solution Prepare a solution of USP Valrubicin RS and USP Valrubicin Related Compound A RS in methanol to obtain a solution having concentrations of about 0.2 mg per mL and 0.05 mg per mL, respectively.
Test solution Use the Assay preparation, prepared as directed in the Assay.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector, a guard column, and a 5-mm × 10-cm analytical column that contains 4-µm packing L1. The flow rate is about 2.5 mL per minute. Chromatograph the Resolution solution, and record the peak areas as directed for Procedure: the relative retention times are about 0.9 for valrubicin related compound A and 1.0 for valrubicin; and the resolution, R, between valrubicin related compound A and valrubicin is not less than 2.
Procedure Inject a volume (about 10 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the areas for the major peaks. Calculate the percentage of each impurity in the portion of Intravesical Solution taken by the formula:
100(ri / rs)in which ri is the peak area for each impurity; and rs is the sum of the peak areas of all the peaks. Do not consider any peaks due to solvent or excipients. Not more than 0.5% of any impurity with a relative retention time of about 0.11 is found; not more than 0.8% of any individual impurity with a relative retention time of 0.16, 0.51 or 0.71 is found; not more than 0.5% of any other individual impurity is found; and the sum of all impurities is not more than 3.5%.
Other requirements It meets the requirements under Injections 1.
Mobile phase Prepare a filtered and degassed mixture of 0.1 M ammonium formate, previously adjusted with formic acid and acetonitrile (55:45) to a pH of 4.0. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation Dissolve an accurately weighed quantity of USP Valrubicin RS in methanol, and quantitatively dilute with methanol to obtain a solution having a known concentration of about 0.2 mg per mL.
Assay preparation Transfer an accurately measured volume of Intravesical Solution, equivalent to about 20 mg of valrubicin, to a 100-mL volumetric flask, dissolve in methanol, dilute with methanol to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector, a guard column, and a 5-mm × 10-cm analytical column that contains 4-µm packing L1. The flow rate is about 2.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2%.
Procedure Separately inject equal volumes (about 10 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, of valrubicin (C34H36 F3NO13) in each mL of the Intravesical Solution taken by the formula:
(CP/V)(rU / rS)in which C is the concentration, in mg per mL, of USP Valrubicin RS in the Standard preparation; P is the specified percentage of valrubicin in USP Valrubicin RS; V is the volume, in mL, of Intravesical Solution taken to prepare the Assay preparation; and rU and rS are the valrubicin peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP32NF27 Page 3841Pharmacopeial Forum: Volume No. 34(6) Page 1486