Zidovudine Capsules

» Zidovudine Capsules 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.

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USP Zidovudine RS

USP Zidovudine Related Compound C RS

Thymine.
C5H6N2O2 126.12

Identification—

A: Ultraviolet Absorption

197U

—

Medium: methanol and water (75:25).

Solution: 15 µg per mL. Obtain the test solution as follows. Mix Capsule contents, equivalent to 300 mg of Zidovudine, with 50 mL of Medium in a 200-mL volumetric flask. Sonicate for 5 minutes, dilute with methanol to volume, and mix. Allow insoluble solids to settle, dilute the supernatant 100-fold with Medium, and mix.

B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation, as obtained in the Assay.

Dissolution

711

—

Medium: water; 900 mL.

Apparatus 2: 50 rpm.

Time: 45 minutes.

Procedure— Determine the amount of C10H13N5O4 dissolved employing the procedure set forth in the Assay, making any necessary modifications.

Tolerances— Not less than 75% (Q) of the labeled amount of C10H13N5O4 is dissolved in 45 minutes.

Uniformity of dosage units

905

: meet the requirements.

Related compounds—

Mobile phase, Standard stock solution, Zidovudine related compound C standard stock solution, and Chromatographic system— Proceed as directed in the Assay.

Standard solution— Proceed as directed for Standard preparation in the Assay.

Test solution— Proceed as directed for Assay preparation in the Assay.

Procedure— Separately inject equal volumes (about 10 µL) of the Standard solution and the Test 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 C is the concentration, in mg per mL, of USP Zidovudine Related Compound C RS in the Standard solution; rU and rS are the peak responses of zidovudine related compound C (thymine) obtained from the Test solution and the Standard solution, respectively; and Q is the quantity, in mg, of zidovudine in the portion of Capsules taken, as determined in the Assay: not more than 3.0% is found.

Assay—

Mobile phase— Prepare a filtered and degassed mixture of water and methanol (80:20). Make adjustments if necessary (see System Suitability under Chromatography

621

Standard stock solution— Dissolve an accurately weighed quantity of USP Zidovudine RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 1.0 mg per mL.

Zidovudine related compound C standard stock solution— Transfer about 20 mg of USP Zidovudine Related Compound C RS, accurately weighed, to a 100-mL volumetric flask, add 75 mL of methanol, sonicate for 15 minutes, dilute with methanol to volume, and mix.

Standard preparation— Transfer 10.0 mL of Standard stock solution and 1.0 mL of Zidovudine related compound C standard stock solution to a 100-mL volumetric flask, add 25 mL of water, mix, dilute with methanol to volume, and mix.

Assay preparation— Weigh the contents of not fewer than 20 Capsules, mix, and transfer an accurately weighed portion of the powder, equivalent to about 100 mg of zidovudine, to a 100-mL volumetric flask. Dissolve in a mixture of methanol and water (75:25), sonicate for 20 minutes, and dilute with a mixture of methanol and water (75:25) to volume. Allow the solids to settle, and transfer 10.0 mL of the supernatant layer to a 100-mL volumetric flask. Dilute with a mixture of methanol and water (75:25) to volume, and filter, discarding the first 4 mL of the filtrate.

Chromatographic system (see Chromatography

621

)— The liquid chromatograph is equipped with a 265-nm detector, a 4.0-mm × 25-cm column that contains packing L1 and a guard column with recommended dimensions of 3.2 mm × 1.5 cm containing packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.2 for zidovudine related compound C (thymine) and 1.0 for 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 10 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 the portion of Capsules taken by the formula:

1000C(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 Assay preparation and the Standard preparation, respectively.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Leonel M. Santos, Ph.D. Senior Scientific Liaison 1-301-816-8168	(SM12010) Monographs - Small Molecules 1
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms

USP35–NF30 Page 5061

Pharmacopeial Forum: Volume No. 34(3) Page 657