Zidovudine Tablets
» Zidovudine Tablets contain not less than 90.0 percent and not more than 110.0 percent 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 11
USP Zidovudine RS. USP Zidovudine Related Compound B RS . USP Zidovudine Related Compound C RS .
Identification
A:
Infrared Absorption 197K
Test specimen
Grind 1 Tablet in a mortar so that no large pieces remain, and remove the coating film so that about 5 mg of ground Tablet remain.
B:
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.
Dissolution 711
Medium:
water; 900 mL.
Apparatus 2:
50 rpm.
Time:
30 minutes.
Procedure
Determine the amount of C10H13N5O4 dissolved by employing the procedure set forth in the Assay, using a filtered portion of the solution under test as the Assay preparation in comparison with a Standard solution having a known concentration of USP Zidovudine RS in the same Medium.
Tolerances
Not less than 80% (Q) of the labeled amount of C10H13N5O4 is dissolved in 30 minutes.
Uniformity of dosage units 905:
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 Suitability under Chromatography 621).
Standard preparation
Prepare as directed in the Assay.
Test preparation
Transfer 1 Tablet to a 100-mL volumetric flask, add about 20 mL of water, and shake by mechanical means to disperse the Tablet. Add about 30 mL of methanol, and sonicate for 10 minutes. Dilute with water to volume, and mix. Pipet 4.0 mL of the resulting solution into a 100-mL volumetric flask, and dilute with water to volume. Mix, and pass a portion of the solution through a suitable nylon filter, discarding the first 2 mL of the filtrate.
Chromatographic system (see Chromatography 621)
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 2.0 mL per 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 10 µL) of the Standard preparation and the Test 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 Tablet taken by the formula:
2500C(rU / rS)
in which C is the concentration, in mg per mL, of USP Zidovudine RS in the Standard preparation; and rU and rS are the peak responses obtained from the Test preparation and the Standard preparation, respectively.
Related compounds
Mobile phase and Chromatographic system
Proceed as directed in the Assay.
Standard solution
Use the Standard preparation, prepared as directed in the Assay.
Test solution
Use the Assay preparation.
Procedure
Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into 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:
100(1/F) (ri / rS)
in which F is the relative response factor and is equal to 1.7 for zidovudine related compound C, and is equal to 1.00 for all other peaks; ri is the peak response for each impurity obtained from the Test solution; and rS is the peak response for zidovudine obtained from the Standard solution: not more than 1.5% of zidovudine related compound C is found; not more than 0.2% of any other individual unidentified impurity is found; and not more than 2.0% of total impurities is found.
Assay
Mobile phase
Dissolve 3.0 g of sodium acetate and 1.3 g of sodium 1-octanesulfonate in 900 mL of water. Add 90 mL of methanol and 40 mL of acetonitrile, and mix. Adjust with glacial acetic acid to a pH of 5.3, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Zidovudine related compound B standard stock solution
Dissolve an accurately weighed quantity of USP Zidovudine Related Compound B RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 0.1 mg per mL.
Zidovudine related compound C standard stock solution
Dissolve by sonicating for about 15 minutes, an accurately weighed quantity of USP Zidovudine Related Compound C RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 0.2 mg per mL.
Standard preparation
Transfer about 30 mg of USP Zidovudine RS, accurately weighed, to a 250-mL volumetric flask, and dissolve in 3.0 mL of methanol. Add 2.5 mL of Zidovudine related compound B standard stock solution, 5.0 mL of Zidovudine related compound C standard stock solution, and dilute with water to volume. This solution contains zidovudine, zidovudine related compound B, and zidovudine related compound C at concentrations of about 0.12 mg per mL, 0.001 mg per mL, and 0.004 mg per mL, respectively.
Assay preparation
Transfer a counted number of Tablets, equivalent to 1500 mg of zidovudine, to a 500-mL volumetric flask. Add about 50 mL of water, and shake by mechanical means for 30 minutes to disperse the Tablets. Add about 150 mL of methanol, and sonicate for 10 minutes. Dilute with water to volume, and mix. Pipet 4.0 mL into a 100-mL volumetric flask, and dilute with water to volume. Mix, and pass a portion of the solution through a suitable nylon filter, discarding the first 2 mL of the filtrate.
Chromatographic system (see Chromatography 621)
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 1.3 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.17 for zidovudine related compound C (thymine), 1.0 for zidovudine, and 1.2 for zidovudine related compound B; the resolution, R, between zidovudine and zidovudine related compound B is 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 20 µL) of the Standard preparation and the Assay preparation into 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 C is the concentration, in mg per mL, of USP Zidovudine RS in the Standard preparation; N is the number of Tablets taken for the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information
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