Gemcitabine for Injection
»Gemcitabine for Injection contains an amount of Gemcitabine Hydrochloride equivalent to not less than 95percent and not more than 105percent of the labeled amount of gemcitabine (C9H11F2N3O4).
Caution—Gemcitabine Hydrochloride is a potent cytotoxic agent.Great care should be taken to prevent inhaling particles and exposing the skin to it.
Packaging and storage— Preserve in Containers for Sterile Solids,as described under Injections á1ñ.Store at controlled room temperature.Do not refrigerate after reconstitution.
USP Reference standards á11ñ— USP Endotoxin RS.USP Gemcitabine Hydrochloride RS.
Identification—
A:Ultraviolet Absorption á197Uñ.
Solution: 16µg per mL.
Medium: 0.14Mphosphate buffer with a pHof 2.5,prepared as follows.Add 13.8g of monobasic sodium phosphate and 2.5mLof phosphoric acid to 1000mLof purified water.
B: 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.
Clarity of solution— Dissolve it in the solvent and at the concentration recommended in the labeling:not more than 10t(see Spectrophotometry and Light-Scattering á851ñ),determined by ratio turbidimetry within 15minutes of reconstitution,corrected for a diluent blank.
Bacterial endotoxins á85ñ— It contains not more than 0.05USP Endotoxin Unit per mg of gemcitabine.
Sterility á71ñ— It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product To Be Examined.
Uniformity of dosage units á905ñ: meets the requirements for Weight Variation.
pHá791ñ: between 2.7and 3.3,in a solution containing 40mg in each mLof 0.9%sodium chloride solution.
Particulate matter á788ñ: meets the requirements for small-volume injections.
Chromatographic purity—
Mobile phase,System suitability solution,Standard solution,and Chromatographic system— Proceed as directed in the test for Chromatographic purityfor Gemcitabine Hydrochloride.
Test solution— Reconstitute the vial with an appropriate amount of water to achieve a solution of 2mg per mL,based on the labeled content of gemcitabine.
Procedure— Proceed as directed in Chromatographic purity for Gemcitabine Hydrochloride.Calculate the amount of cytosine expressed as a percentage of Gemcitabine Hydrochloride by the formula:
0.1(263.20/299.66)(CcV/L)(rt /rs )
in which 263.20and 299.66are the molecular weights of gemcitabine and gemcitabine hydrochloride,respectively;Ccis the concentration of USP Cytosine RSin the Standard solution,in µg per mL;Vis the volume,in mL,of water used to reconstitute the vial;Lis the labeled amount of gemcitabine in the vial,in mg;rtis the peak response for cytosine in the Test solution;and rsis the response for cytosine in the Standard solution:not more than 0.1%of cytosine is found.Similarly,calculate the amount of each impurity other than cytosine,expressed as a percentage of gemcitabine hydrochloride,by the formula:
0.1(263.20/299.66)(CsV/L)(ri/rs)
in which 263.20and 299.66are the molecular weights of gemcitabine and gemcitabine hydrochloride,respectively;Csis the concentration of USP Gemcitabine Hydrochloride RSin the Standard solution,in µg per mL;Vis the volume,in mL,of water used to reconstitute the vial,Lis the labeled amount of gemcitabine in the vial,in mg;riis the response for gemcitabine a-anomer or any other individual impurity;and rsis the peak response for gemcitabine in the Test solution.Not more than 0.1%of gemcitabine a-anomer is found;not more than 0.2%each of any other impurity is found;and the sum of all impurities is not more than 0.3%.Exclude from the sum of all impurities any peaks that are below the limit of quantitation (0.02%).
Assay—
Mobile phase,System suitability solution,Standard preparation,and Chromatographic system— Proceed as directed in the Assayunder Gemcitabine Hydrochloride.
Assay preparation— Constitute a suitable number of vials of Gemcitabine for Injection with purified water to obtain a solution having a concentration of about 0.1mg per mL,based on the labeled content of gemcitabine.
Procedure— Proceed as directed in the Assayunder Gemcitabine Hydrochloride.Calculate the amount,in mg,of gemcitabine (C9H11F2N3O4)in each vial of Gemcitabine for Injection taken by the formula:
(263.20/299.66)(CV/N)(rU/rS),
in which 263.20and 299.66are the molecular weights of gemcitabine and gemcitabine hydrochloride,respectively;Vis the total volume,in mL,of the Assay preparation;Nis the number of vials taken;and the other terms are as defined therein.
Auxiliary Information— Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28–NF23Page 893
Pharmacopeial Forum:Volume No.30(4)Page 1246
Phone Number:1-301-816-8389