Zidovudine Tablets »Zidovudine Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amount of zidovudine (C10H13N5O4). Packaging and storage— Preserve in tight,light-resistant containers,and store at controlled room temperature. USP Reference standards á11ñ USP Zidovudine RS. Identification— A:Infrared Absorption á197Kñ Test specimen— Grind 1Tablet in a mortar so that no large pieces remain,and remove the coating film so that about 5mg of ground Tablet remain. 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. Dissolution á711ñ Medium: water;900mL. Apparatus 2: 50rpm. Time: 30minutes. Procedure— Determine the amount of C10H13N5O4dissolved by employing the procedure set forth in the Assay,using a filtered portion of the solution under test as the Assay preparationin comparison with a Standard solution having a known concentration of USP Zidovudine RSin the same Medium. Tolerances— Not less than 80%(Q)of the labeled amount of C10H13N5O4is dissolved in 30minutes. Uniformity of dosage units á905ñ: meet the requirements. PROCEDURE FOR CONTENT UNIFORMITY Mobile phase— Prepare a filtered and degassed mixture of water and methanol (4:1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Standard preparation— Prepare as directed in the Assay. Test preparation— Transfer 1Tablet to a 100-mLvolumetric flask,add about 20mLof water,and shake by mechanical means to disperse the Tablet.Add about 30mLof methanol,and sonicate for 10minutes.Dilute with water to volume,and mix.Pipet 4.0mLof the resulting solution into a 100-mLvolumetric flask,and dilute with water to volume.Mix,and pass a portion of the solution through a suitable nylon filter,discarding the first 2mLof the filtrate. Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 265-nm detector and a 4.6-mm ×15-cm column that contains base-deactivated packing L1.The flow rate is about 2.0mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure: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 Test preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of zidovudine (C10H13N5O4)in the Tablet taken by the formula: 2500C(rU/rS), in which Cis the concentration,in mg per mL,of USP Zidovudine RSin the Standard preparation;and rUand rSare the peak responses obtained from the Test preparationand the Standard preparation,respectively. Related compounds— Mobile phase,Standard preparation,andChromatographic system— Proceed as directed in the Assay. Test preparation— Use the Assay preparation. Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Test preparationinto the chromatograph,record the chromatograms,and measure all of the peak responses.Calculate the percentage of each impurity in the portion of Tablets taken by the formula: 100F(ri/rS), in which Fis the relative response factor and is equal to 0.59for any peak with a relative retention time of 0.17,and is equal to 1.00for all other peaks;riis the peak response for each impurity obtained from the Test preparation;and rSis the peak response for zidovudine obtained from the Standard preparation:not more than 1.5%of an impurity with a relative retention time of 0.17is found;not more than 0.2%of any other impurity is found;and not more than 2.0%of total impurities is found. Assay— Mobile phase— Dissolve 3.0g of sodium acetate and 1.3g of sodium 1-octanesulfonate in 900mLof water.Add 90mLof methanol and 40mLof acetonitrile,and mix.Adjust with glacial acetic acid to a pHof 5.3,filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Standard preparation— Dissolve an accurately weighed quantity of USP Zidovudine RSin a volume of methanol,equivalent to not more than 1.2%of the total flask volume,dilute with water to volume,and mix to obtain a final solution having a known concentration of about 0.12mg per mL. Assay preparation— Transfer a counted number of Tablets,equivalent to 1500mg of zidovudine,to a 500-mLvolumetric flask.Add about 50mLof water,and shake by mechanical means for 30minutes to disperse the Tablets.Add about 150mLof methanol,and sonicate for 10minutes.Dilute with water to volume,and mix.Pipet 4.0mLinto a 100-mLvolumetric flask,and dilute with water to volume.Mix,and pass a portion of the solution through a suitable nylon filter,discarding the first 2mLof the filtrate. Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 265-nm detector and a 4.6-mm ×15-cm column that contains packing L1.The flow rate is about 1.3mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the resolution,R,between zidovudine and a peak having a relative retention time of about 1.2is not less than 2.5;the tailing factor for the zidovudine peak 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 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of zidovudine (C10H13N5O4)in each Tablet taken by the formula: 12,500(C/N)(rU/rS), in which Cis the concentration,in mg per mL,of USP Zidovudine RSin the Standard preparation;Nis the number of Tablets taken for the Assay preparation;and rUand rSare the peak responses 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 2050 Pharmacopeial Forum:Volume No.27(4)Page 2787 Phone Number:1-301-816-8394