Zidovudine Capsules »Zidovudine Capsules 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. USP Reference standards á11ñ USP Zidovudine RS.USP Zidovudine Related Compound C RS. Identification— A:Ultraviolet Absorption á197Uñ Medium: methanol and water (75:25). Solution: 15µg per mL.Obtain the test solution as follows.Mix Capsule contents,equivalent to 300mg of Zidovudine,with 50mLofMedium in a 200-mLvolumetric flask.Sonicate for 5minutes,dilute with methanol to volume,and mix.Allow insoluble solids to settle,dilute the supernatant 100-fold withMedium,and mix. B: The retention time of the major peak in the chromatogram of theAssay preparation corresponds to that of theStandard preparation,as obtained in theAssay. Dissolution á711ñ Medium: water;900mL. Apparatus 2: 50rpm. Time: 45minutes. Procedure— Determine the amount of C10H13N5O4dissolved employing the procedure set forth in theAssay,making any necessary modifications. Tolerances— Not less than 75%(Q)of the labeled amount of C10H13N5O4is dissolved in 45minutes. Uniformity of dosage units á905ñ: meet the requirements. Related compounds— Mobile phase,Standard stock solution,Zidovudine related compound Cstandard stock solution,and Chromatographic system— Proceed as directed in theAssay under Zidovudine. Standard solution— Proceed as directed forStandard preparation in theAssay. Test solution— Proceed as directed forAssay preparation in theAssay. Procedure— Separately inject equal volumes (about 10µL)of theStandard solution and theTest solution into the chromatograph,record the chromatograms,and measure the peak responses.Calculate the quantity,in mg,of zidovudine related compound C(thymine)in the portion of Capsules taken by the formula: 1000C[(rU/rS)/Q], in which Cis the concentration,in mg per mL,of USP Zidovudine Related Compound C RSin theStandard solution;rUand rSare the peak responses of zidovudine related compound C(thymine)obtained from theTest solution and theStandard solution,respectively;andQis the quantity,in mg,of zidovudine in the portion of Capsules taken,as determined in theAssay:not more than 3.0%is found. Assay— Mobile phase,Standard stock solution,and Zidovudine related compound Cstandard stock solution— Prepare as directed in theAssay under Zidovudine. Standard preparation— Transfer 10.0mLofStandard stock solution and 1.0mLofZidovudine related compound Cstandard stock solution to a 100-mLvolumetric flask,add 25mLof water,mix,dilute with methanol to volume,and mix. Assay preparation— Weigh the contents of not fewer than 20Capsules,mix,and transfer an accurately weighed portion of the powder,equivalent to about 100mg of zidovudine,to a 100-mLvolumetric flask.Dissolve in a mixture of methanol and water (75:25),sonicate for 20minutes,and dilute with a mixture of methanol and water (75:25)to volume.Allow the solids to settle,and transfer 10.0mLof the supernatant layer to a 100-mLvolumetric flask.Dilute with a mixture of methanol and water (75:25)to volume,and filter,discarding the first 4mLof the filtrate. Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 265-nm detector and a 4.0-mm ×25-cm column that contains packing L1and a 3.2-mm ×1.5-cm guard column containing packing L1.The flow rate is about 1.0mLper minute.Chromatograph theStandard preparation,and record the peak responses as directed forProcedure:the relative retention times are about 0.2for zidovudine related compound C(thymine)and 1.0for zidovudine;the resolution,R,between zidovudine and zidovudine related compound C(thymine)is not less than 5.0;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 theStandard preparation and theAssay preparation into the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of zidovudine (C10H13N5O4)in the portion of Capsules taken by the formula: 1000C(rU/rS), in whichCis the concentration,in mg per mL,of USP Zidovudine RSin theStandard preparation;and rUand rSare the peak responses obtained from theAssay preparation and theStandard preparation,respectively. Auxiliary Information— Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist Expert Committee:(PA7)Pharmaceutical Analysis 7 USP28–NF23Page 2048 Pharmacopeial Forum:Volume No.27(5)Page 3058 Phone Number:1-301-816-8394