Lamivudine and Zidovudine Tablets

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

Lamivudine and Zidovudine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of lamivudine (C₈H₁₁N₃O₃S) and zidovudine (C₁₀H₁₃N₅O₄).

2 IDENTIFICATION

A. The retention times of the lamivudine and zidovudine peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

Add the following:

B. The UV spectrum of the major 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

Solution A: 25 mM of ammonium acetate. Adjust with glacial acetic acid to a pH of 4.0.

Solution B: Methanol

Solution C: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Solution A and Solution B (19:1)

System suitability solution: 0.17 mg/mL of USP Lamivudine Resolution Mixture B RS in Diluent

Standard solution: 0.15 mg/mL of USP Lamivudine RS and 0.30 mg/mL of USP Zidovudine RS in Diluent

Sample stock solution: Transfer a counted number of Tablets, equivalent to 1500 mg of zidovudine and 750 mg of lamivudine, to a 500-mL volumetric flask. Add 250 mL of water and disintegrate the Tablets completely by shaking for a minimum of 15 min. Dilute with water to volume, and mix.

Sample solution: Pass a portion of the Sample stock solution through a filter of 0.45-μm pore size, discarding the first 2–3 mL. Further dilute the filtrate to obtain 0.15 mg/mL of lamivudine and 0.30 mg/mL of zidovudine in Diluent.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 270 nm. For Identi

cation B, use a diode array detector in the range of 200–400 nm. (USP 1-May-2022)

Column: 3-mm × 25-cm; packing L1

Flow rate: 0.5 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for lamivudine diastereomer and lamivudine are 0.50 and 0.52, respectively.]

Suitability requirements

Resolution: NLT 1.5 between lamivudine diastereomer and lamivudine, System suitability solution

Relative standard deviation: NMT 2.0% for zidovudine and lamivudine, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lamivudine (C₈H₁₁N₃O₃S) and zidovudine (C₁₀H₁₃N₅O₄) in the portion of Tablets taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of zidovudine or lamivudine from the Sample solution

r_S = peak response of zidovudine or lamivudine from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Test 1

Medium: 0.1 N hydrochloric acid; 900 mL, deaerated

Apparatus 2: 75 rpm

Time: 15 min

Lamivudine standard (USP 1-May-2022) solution: 0.167 mg/mL of USP Lamivudine RS in Medium. [Note—Prepare in duplicate.]

Zidovudine standard (USP 1-May-2022) solution: 0.333 mg/mL of USP Zidovudine RS in Medium. [Note—Prepare in duplicate.]

Sample solution: Pass a portion of the solution under test through a suitable filter (PTFE, PVDF, or equivalent) of 0.45-μm pore size.

Detector: UV 240–300 nm

Blank: Medium

Cell: 0.02 cm, flow-cell

Analysis: The calculations of the percentages dissolved are done using a multicomponent analysis software.

Tolerances: NLT 85% (Q) of the labeled amount of zidovudine and lamivudine is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Buffer solution: 7.7 g/L of ammonium acetate in water

Mobile phase: Acetonitrile and Buffer solution (1:9)

Standard stock solution: 1.4 mg/mL of USP Lamivudine RS and 2.8 mg/mL of USP Zidovudine RS in Medium. A small amount of methanol,

NMT 20% of the

nal volume, can be used to dissolve both compounds.

Standard solution: 0.168 mg/mL of lamivudine and 0.336 mg/mL of zidovudine in Medium from the Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 270 nm

Column: 4.6-mm × 15-cm; packing L1

Column temperature: 40°

Flow rate: 1.2 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 1500 theoretical plates for lamivudine and NLT 3000 theoretical plates for zidovudine

Tailing factor: NMT 2.0 for lamivudine and zidovudine

Relative standard deviation: NMT 2.0% for zidovudine and lamivudine

Calculate the percentage of lamivudine (C₈H₁₁N₃O₃S) and zidovudine (C₁₀H₁₃N₅O₄) dissolved:

Result = (r_U/r_S)x(C_S/L) × V × 100

r_U= peak response of lamivudine or zidovudine from the Sample solution

r_S = peak response of lamivudine or zidovudine from the Standard solution

C_S = concentration of lamivudine or zidovudine in the Standard solution (mg/mL)

L = label claim for lamivudine or zidovudine (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of zidovudine and lamivudine is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements for zidovudine and lamivudine

5 IMPURITIES

5.1 Organic Impurities

Solution A, Solution B, Solution C, Mobile phase, Diluent, System suitability solution, Sample solution, Chromatographic system, and

System suitability: Proceed as directed in the Assay.

5.2 Analysis

Sample: Sample solution

Calculate the percentage of each lamivudine-related impurity in the portion of Tablets taken:

Result = (r_U/r_T) × 100

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

r_T = sum of the peak responses of lamivudine and all lamivudine-related impurities from the Sample solution

Calculate the percentage of each zidovudine-related impurity and unspecified impurity in the portion of Tablets taken:

Result = (r_U/r_T) × (1/F) × 100

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

r_T = sum of the peak responses of zidovudine, all zidovudine-related impurities, and unspecified impurities from the Sample solution

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a 4-Aminopyrimidin-2(1H)-one.

^b The individual impurity limit is not included because these are process/other impurities monitored individually in the drug substances.

^c Pyrimidine-2,4(1H,3H)-dione.

^d (2R,5S)-5-(4-Amino-2-oxopyrimidin-1(2H)-yl)-1,3-oxathiolane-2-carboxylic acid (2R,5S)-5-(cytosine-1-yl)-1,3-oxathiolane-2-carboxylic acid.

^e 1-[(2R,3S,5S)-2-(Hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine S-oxide.

^f 1-[(2R,3R,5S)-2-(Hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine S-oxide.

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

^h 1-[(2S,5S)-2-(Hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine.

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

^j (2RS,5SR)1-[(2R,5S)-2-(Hydroxymethyl)-1,3-oxathiolan-5-yl]uracil.

^k 2-Hydroxybenzoic acid.

l 3'-Chloro-3'-deoxythymidine.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, protected from light, and store between 2° and 30°.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Lamivudine RS

USP Lamivudine Resolution Mixture B RS

USP Zidovudine RS