Zidovudine Oral Solution

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Zidovudine Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of zidovudine (C₁₀H₁₃N₅O₄).

2 IDENTIFICATION

Change to read:

A. (USP 1-May-2022) The retention time of the zidovudine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Add the following:

B. The UV spectrum of the zidovudine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.(USP 1-May-2022)

3 ASSAY

Change to read:

Procedure

Mobile phase: Methanol, acetonitrile, glacial acetic acid, and 0.040 M sodium acetate (90:10:2:900)

Standard stock solution: 1 mg/mL of USP Zidovudine RS in Mobile phase

Zidovudine related compound C stock solution: 0.1 mg/mL of USP Zidovudine Related Compound C RS in Mobile phase. [Note—Sonicate for 10 min before making nal volume.]

Standard solution: Transfer 10.0 mL of the Standard stock solution and 2.0 mL of Zidovudine related compound C stock solution to a 100-mL volumetric ask. Dilute with Mobile phase to volume.

Sample solution: Nominally 0.1 mg/mL of zidovudine in Mobile phase

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm. For Identification B, use a diode array detector in the range of 200–400 nm. (USP 1-May-2022) Column: 4.0-mm × 12.5-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

3.2 System suitability

Sample: Standard solution

[Note—The relative retention times for zidovudine related compound C and zidovudine are about 0.12 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 4.0 between zidovudine and zidovudine related compound C

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zidovudine (C₁₀H₁₃N₅O₄) in the portion of Oral Solution taken: 

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Zidovudine RS in the Standard solution (mg/mL)

C_U = nominal concentration of zidovudine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Change to read:

[Note—On the basis of knowledge of the product, (USP 1-May-2022) perform either Organic Impurities, Procedure 1 or Procedure 2.] •

4.1 Organic Impurities, Procedure 1

Mobile phase, Standard stock solution, Zidovudine related compound C solution, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of zidovudine related compound C in the portion of Oral Solution taken:

Result = (r_U/r_S ) × (C_S /C_U ) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Zidovudine Related Compound C RS in the Standard solution (mg/mL)

C_U = nominal concentration of zidovudine in the Sample solution (mg/mL)

Acceptance criteria: NMT 3.0%

Change to read:

4.2 Organic Impurities, Procedure 2

Buffer: 5.44 mg/mL of sodium acetate trihydrate in water. Pass the solution through a suitable lter of 0.45-µm pore size. Mobile phase: Methanol, acetonitrile, glacial acetic acid, and Buffer (50:10:2:940)

Impurity stock solution: 0.625 mg/mL of USP Zidovudine Related Compound C RS, 0.375 mg/mL of thymidine, 0.375 mg/mL of USP Stavudine RS, and 0.25 mg/mL of USP Zidovudine Related Compound B RS dissolved initially with methanol at 25% of the nal volume. Dilute with Mobile phase to nal volume. [Note—Sonicate with intermittent shaking to dissolve, if necessary, and cool to room temperature before diluting to nal volume.]

Impurity solution: 0.05 mg/mL of USP Zidovudine Related Compound C RS, 0.03 mg/mL of thymidine, 0.03 mg/mL of USP Stavudine RS, and 0.02 mg/mL of USP Zidovudine Related Compound B RS in Mobile phase from the Impurity stock solution

System suitability solution: 1 mg/mL of USP Zidovudine RS, 0.005 mg/mL of USP Zidovudine Related Compound C RS, 0.003 mg/mL of thymidine, 0.003 mg/mL of USP Stavudine RS, and 0.002 mg/mL of USP Zidovudine Related Compound B RS in Mobile phase from USP Zidovudine RS and the Impurity solution

Standard stock solution: 0.25 mg/mL of USP Zidovudine RS in Mobile phase. Sonicate to dissolve, if necessary. Standard solution: 0.002 mg/mL of USP Zidovudine RS in Mobile phase from the Standard stock solution

Sample solution: Nominally 1 mg/mL of zidovudine in Mobile phase

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 10-cm; 3-µm packing L1

Column temperature: 25°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

4.2.2 System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 1 for relative retention times.]

Suitability requirements

Resolution: NLT 1.4 between zidovudine and zidovudine related compound B, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution (USP 1-May-2022)

4.2.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Oral Solution taken:

Result = (r_U /r_S ) × (C_S /C_U ) × (1/F) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of zidovudine from the Standard solution

C_S = concentration of USP Zidovudine RS in the Standard solution (mg/mL)

C_U = nominal concentration of zidovudine in the Sample solution (mg/mL)

F = relative response factor for each individual impurity (see Table 1)

Acceptance criteria: See Table 1.

Table 1

a [1-(2-Deoxy-β- d-ribofuranosyl)]thymine.

b 1-(2,3-Dideoxy-β-d-glyceropent-2-enofuranosyl)thymine. (USP 1-May-2022)

c Excludes zidovudine related compound C.

5 SPECIFIC TESTS

Change to read:

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count is NMT 102 cfu/mL, and the total yeasts and molds count is NMT 101 cfu/mL. (USP 1-May-2022) Meets the requirements of the tests for absence of Salmonella species, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.

pH 〈791〉

Sample: A mixture containing a volume of Oral Solution equivalent to 150 mg of zidovudine and 5 mL of 0.12 M potassium chloride (3:1) Acceptance criteria: 3.0–4.0

6 PERFORMANCE TESTS

Deliverable Volume 〈698〉

For multiple-unit containers: Meets the requirements

Uniformity of Dosage Units 〈905〉

For single-unit containers: Meets the requirements

7 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.(USP 1-May-2022)

Labeling: If a test for Organic Impurities other than Procedure 1 is used, then the labeling states with which Organic Impurities test the article complies.

Change to read:

USP Reference Standards 〈11〉

USP Stavudine RS

USP Zidovudine RS

USP Zidovudine Related Compound B RS

3′-Chloro-3′-deoxythymidine.

C₁₀H₁₃ClN₂O₄     260.67 (USP 1-May-2022)

USP Zidovudine Related Compound C RS

Thymine;

5-Methylpyrimidine-2,4(1H,3H)-dione.

C₅H₆N₂O₂  126.11 (USP 1-May-2022)