Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Nucleoside reverse transcriptase inhibitor; antiviral (HIV).
DEFINITION
Lamivudine Tablets contain Anhydrous Lamivudine.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of lamivudine, C8H11N3O3S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
To a quantity of the powdered tablets containing 50 mg of Anhydrous Lamivudine add 20 mL of methanol, shake, filter and evaporate the filtrate to dryness. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of lamivudine (RS 451).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2 and rotate the paddle at 50 revolutions per minute.
(b) Use 900 mL of 0.1M hydrochloric acid, at a temperature of 37°, as the medium.
PROCEDURE
(1) After 45 minutes withdraw a sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maximum at 280 nm, Appendix II B, using dissolution medium in the reference cell.
(2) Measure the absorbance of a suitable solution of lamivudine BPCRS using dissolution medium in the reference cell.
DETERMINATION OF CONTENT
Calculate the total content of lamivudine, C8H11N3O3S, in the medium from the absorbances obtained and using the declared content of C8H11N3O3S in lamivudine BPCRS.
LIMITS
The amount of lamivudine released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 0.3 g of Anhydrous Lamivudine in 60 mL of water with the aid of ultrasound for 30 minutes, dilute to 100 mL and filter. Dilute 1 volume of the filtrate to 10 volumes with the mobile phase.
(2) Dilute 1 volume of solution (1) to 50 volumes with the mobile phase and further dilute 1 volume to 10 volumes with the mobile phase.
(3) Dilute 1 volume of solution (2) to 2 volumes with the mobile phase.
(4) 0.03% w/v of lamivudine impurity standard BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Hypersil BDS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use a column temperature of 35°.
(e) Use a detection wavelength of 277 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
5 volumes of methanol and 95 volumes of 0.025M ammonium acetate, the pH of the aqueous component having previously been adjusted to 4.0 with glacial acetic acid.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4):
the chromatogram closely resembles the reference chromatogram supplied with lamivudine impurity standard BPCRS;
the resolution factor between the peaks due to lamivudine impurity B and lamivudine is at least 2.0.
LIMITS
Using the chromatogram obtained with solution (4) and the reference chromatogram supplied with lamivudine impurity standard BPCRS identify any peaks in solution (1) corresponding to impurity A and impurity B.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to lamivudine impurity A is not greater than 1.5 times the area of the peak due to lamivudine in the chromatogram obtained with solution (2) (0.3%);
the area of any peak corresponding to lamivudine impurity B is not greater than the area of the peak due to lamivudine in
the chromatogram obtained with solution (2) (0.2%);
the area of any other secondary peak is not greater than the area of the peak due to lamivudine in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of all the secondary peaks is not greater than 3 times the area of the peak due to lamivudine in the chromatogram obtained with solution (2) (0.6%).
Disregard any peak with an area less than the area of the peak in the chromatogram obtained with solution (3) (0.1%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 0.3 g of Anhydrous Lamivudine in 60 mL of water with the aid of ultrasound for 30 minutes, dilute to 100 mL with the mobile phase and filter. Dilute 1 volume of the filtrate to 10 volumes with the mobile phase.
(2) 0.03% w/v of lamivudine BPCRS in the mobile phase.
(3) 0.03% w/v of lamivudine impurity standard BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3):
the resolution factor between the peaks due to lamivudine impurity B and lamivudine is at least 2.0.
DETERMINATION OF CONTENT
Calculate the content of C8H11N3O3S in the tablets using the declared content of C8H11N3O3S in lamivudine BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A, B, C, E, F, G, H, I and J listed under Anhydrous Lamivudine.
