Lamivudine 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

Lamivudine Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of lamivudine (C₈H₁₁N₃O₃S). It may contain a suitable preservative.

2 IDENTIFICATION

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

3 ASSAY

Change to read:

Procedure

Solution A: 2.0 g/L of sodium heptanesulfonate in water. Add 1.0 mL of hydrochloric acid and 1.0 mL of triethylamine per L of the solution.

Solution B: Acetonitrile and Solution A (50:50)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (10:90)

System suitability solution: Dissolve the contents of 1 vial of USP Lamivudine Resolution Mixture C RS in 2.5 mL of Diluent.

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

Sample solution: Nominally 0.2 mg/mL of lamivudine in water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 277 nm

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

Flow rate: 1 mL/min (ERR 1-Jun-2018)

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between lamivudine-S-sulfoxide and lamivudine-R-sulfoxide, System suitability solution

Tailing factor: NMT 2.0 for the lamivudine peak, System suitability solution

Relative standard deviation: NMT 2% for the lamivudine peak, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of lamivudine from the Sample solution

r_S = peak response of lamivudine 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

Deliverable Volume 〈698〉: Meets the requirements

5 IMPURITIES

5.1 Organic Impurities

Solution A, Solution B, 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 any individual impurity in the portion of Oral Solution taken:

Result = (r_U/r_T) × 100

r_U = peak response of each individual impurity

r_T = sum of the responses of all of the peaks excluding peaks due to added preservative(s) or excipients

Acceptance criteria: See Table 2.

Table 2

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

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

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

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

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

^f This impurity is controlled in the drug substance and is not to be included in the total impurities. Disregard any peak less than 0.01%.

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

6 SPECIFIC TESTS

pH 〈791〉: 5.7–6.3

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count does not exceed 102

cfu/mL.

The total molds and yeasts count does not exceed 102

cfu/mL. It meets the requirements of the test for absence of Escherichia coli.

ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in light-resistant containers at controlled room temperature.

USP Reference Standards 〈11〉

USP Lamivudine RS

USP Lamivudine Resolution Mixture C RS

[Note—This reference standard contains lamivudine and several related impurities.]