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

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M (CN 1-May-2020)

Sample: Crush 1 Tablet and transfer it to a suitable container. Add 5 mL of methanol and shake for 15 min. Pass through a suitable filter, collecting about 2 mL of the filtrate. Evaporate the filtrate to dryness under a gentle stream of nitrogen, and use the residue.

Standard: Dissolve a suitable amount of USP Lamivudine RS in a small amount of methanol, shaking until completely dissolved. Evaporate to dryness under a gentle stream of nitrogen, and use the residue.

Acceptance criteria: Meet the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: 1.9 g/L of ammonium acetate in water. Adjust with acetic acid to a pH of 3.8.

Mobile phase: Methanol and Buffer (50:950)

System suitability solution: 0.2 mg/mL of USP Lamivudine Resolution Mixture B RS in Mobile phase

Standard solution: 0.2 mg/mL of USP Lamivudine RS in Mobile phase

Sample stock solution: Nominally about 3–4 mg/mL of lamivudine in water prepared as follows. Transfer the required number of Tablets, based on the labeled amount, to a suitable volumetric flask, and soak or shake for at least 15 min in water to disperse the sample. Dilute with water to volume, mix, and pass through a suitable filter or centrifuge.

Sample solution: Nominally 0.2 mg/mL of lamivudine in Mobile phase from the Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 277 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Column temperature: 30 ± 5°

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for lamivudine diastereomer and lamivudine are 0.9 and 1.0, respectively.]

Suitability requirements

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

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S)x(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 Lamivudine RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Procedure for products labeled as Lamivudine Tablets 100-mg or 150-mg

Medium: Water, degassed; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: (L/900) mg/mL of USP Lamivudine RS in Medium, where L is the Tablet label claim in mg

Sample solution: Pass a portion of the solution under test through a suitable filter to obtain a concentration similar to that of the Standard solution.

Instrumental conditions

Mode: UV

Analytical wavelength: 270 nm

Cell: 1 mm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lamivudine (C₈H₁₁N₃O₃S) dissolved:

Result = (A_U/A_S) × C_S × V × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of lamivudine (C₈H₁₁N₃O₃S) is dissolved.

Procedure for products labeled as Lamivudine Tablets 300-mg

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 75 rpm

Time: 15 min

Standard solution: (L/900) mg/mL of USP Lamivudine RS in Medium, where L is the Tablet label claim in mg

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

Instrumental conditions

Mode: UV

Analytical wavelength: 280 nm

Cell: 0.5 mm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lamivudine (C₈H₁₁N₃O₃S) dissolved:

Result = (A_U/A_S) × C_S × V × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of lamivudine (C₈H₁₁N₃O₃S) 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: 50 rpm

Time: 15 min

Buffer: 1.93 g/L of ammonium acetate in water. Adjust with glacial acetic acid to a pH of 3.8.

Mobile phase: Methanol and Buffer (40:60)

Standard solution: (L/900) mg/mL of USP Lamivudine RS in Medium, where L is the Tablet label claim in mg

Sample solution: Pass a portion of the solution under test through a suitable filter to obtain a concentration similar to that of the Standard solution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: 285 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 5 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

Tailing factor: NMT 1.5

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lamivudine (C₈H₁₁N₃O₃S) dissolved:

Result = (r_U/r_S) × C_S × V × (1/L) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of lamivudine (C₈H₁₁N₃O₃S) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Buffer, Mobile phase, System suitability solution, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Sample: Sample solution

Calculate the percentage of each individual impurity in the portion of Tablets taken:

Result = (r_U/r_T) × 100

r_U = peak response of each individual impurity

r_T = sum of all the peak responses

Acceptance criteria: See Table 1.

Table 1

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

^b (2RS,5SR)-5-(Cytosine-1-yl)-1,3-oxathiolane-2-carboxylic acid.

^c Process impurity included in the table for identification only. Process impurities are controlled in the drug substance and are not to be reported or included in the total impurities for the drug product.

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

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

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

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at room temperature.

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

[Note—The resolution mixture contains lamivudine and lamivudine diastereomer. Other impurities may also be present.]