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Ganciclovir for Injection
» Ganciclovir for Injection is a freeze-dried powder prepared by the neutralization of Ganciclovir with the aid of Sodium Hydroxide. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of ganciclovir (C9H13N5O4), calculated on the anhydrous basis.
Caution—Handle Ganciclovir for Injection with great care, as it is a potent cytotoxic agent and suspected carcinogen.
Packaging and storage— Preserve in Containers for Sterile Solids, as described under Injections 1. Store between 15 and 30, unless otherwise specified by the manufacturer. Protect from moisture.
Labeling— Label it to state that it is to be handled with great care because it is a potent cytotoxic agent and suspected carcinogen.
Constituted solution— At the time of use, it meets the requirements for Constituted Solutions under Injections 1.
Identification— 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— It contains not more than 0.84 Endotoxin Unit per mg of Ganciclovir for Injection.
Sterility 71— It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product To Be Examined.
pH 791: between 10.8 and 11.4, in the solution constituted as directed in the labeling.
Water, Method I 921— Proceed as directed in the chapter, except to use the following modifications. Use a mixture of anhydrous formamide and methanol (1:1) in place of methanol as the titration vessel solvent. The Reagent volume required in order to condition the titration vessel solvent is not greater than 10% of the initial volume of solvent. The concentration of Ganciclovir for Injection in the titration vessel is not greater than 7 mg per mL. Not more than 3.0% is found.
Particulate matter 788: meets the requirements for small-volume injections.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay—
Mobile phase— Dissolve 1.4 g of monobasic ammonium phosphate and 2.0 g of phosphoric acid in 500 mL of water in a 1000-mL volumetric flask. Dilute with water to volume, mix, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Internal standard solution— Transfer about 75 mg of hypoxanthine to a 500-mL volumetric flask, dissolve in and dilute with water to volume, and mix.
Standard stock preparation— Dissolve an accurately weighed amount of USP Ganciclovir RS in water to obtain a solution having a known concentration of about 250 µg per mL.
Standard preparation— Transfer 20.0 mL of the Standard stock preparation and 10.0 mL of the Internal standard solution to a 100-mL volumetric flask. Dilute with Mobile phase to volume, and mix.
Assay stock preparation— Constitute Ganciclovir for Injection in a portion of water, quantitatively transfer with water to a suitable volumetric flask, and dilute with water to volume to obtain a solution having a concentration of about 1 mg per mL.
Assay preparation— Transfer 5.0 mL of the Assay stock preparation and 10.0 mL of the Internal standard solution to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 10-cm column that contains packing L1. The flow rate is about 1.2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for hypoxanthine and 1.0 for ganciclovir; the resolution, R, between hypoxanthine and ganciclovir is not less than 3.0; the column efficiency is not less than 1000 theoretical plates; the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
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 peak response ratios for the major peaks. Calculate the quantity, in mg, of ganciclovir (C9H13N5O4) in the container of Ganciclovir for Injection taken by the formula:
CD(RU / RS),
in which C is the concentration, in mg per mL, of USP Ganciclovir RS in the Standard preparation; D is the dilution factor, in mL, used to prepare the Assay preparation; and RU and RS are the peak response ratios of ganciclovir to the internal standard obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Behnam Davani, Ph.D., MBA, Senior Scientist
Expert Committee : (MDAA05) Monograph Development-Antivirals and Antimicrobials
USP29–NF24 Page 987
Pharmacopeial Forum : Volume No. 29(3) Page 630
Phone Number : 1-301-816-8394