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 90.0percent and not more than 110.0percent 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 á1ñ.Store between 15and 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 Solutionsunder Injections á1ñ.
Identification— The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
Bacterial endotoxins á85ñ— It contains not more than 0.84Endotoxin Unit per mg of Ganciclovir for Injection.
Sterility á71ñ— It meets the requirements when tested as directed for Membrane Filtrationunder Test for Sterility of the Product To Be Examined.
pHá791ñ: between 10.8and 11.4,in the solution constituted as directed in the labeling.
Water,Method Iá921ñ— 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 Reagentvolume 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 7mg per mL.Not more than 3.0%is found.
Particulate matter á788ñ: meets the requirements for small-volume injections.
Assay—
Mobile phase— Dissolve 1.4g of monobasic ammonium phosphate and 2.0g of phosphoric acid in 500mLof water in a 1000-mLvolumetric flask.Dilute with water to volume,mix,filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Internal standard solution— Transfer about 75mg of hypoxanthine to a 500-mLvolumetric flask,dissolve in and dilute with water to volume,and mix.
Standard stock preparation— Dissolve an accurately weighed amount of USP Ganciclovir RSin water to obtain a solution having a known concentration of about 250µg per mL.
Standard preparation— Transfer 20.0mLof the Standard stock preparationand 10.0mLof the Internal standard solutionto a 100-mLvolumetric flask.Dilute with Mobile phaseto 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 1mg per mL.
Assay preparation— Transfer 5.0mLof the Assay stock preparationand 10.0mLof the Internal standard solutionto a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)— 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 1.2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.7for hypoxanthine and 1.0for ganciclovir;the resolution,R,between hypoxanthine and ganciclovir is not less than 3.0;the column efficiency is not less than 1000theoretical 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 10µL)of the Standard preparationand the Assay preparationinto 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 Cis the concentration,in mg per mL,of USP Ganciclovir RSin the Standard preparation;Dis the dilution factor,in mL,used to prepare the Assay preparation;and RUand RSare the peak response ratios of ganciclovir to the internal standard obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 890
Pharmacopeial Forum:Volume No.29(3)Page 630
Phone Number:1-301-816-8394