- British Pharmacopoeia Volume III
- Formulated Preparations: Specific Monographs
Losartan Potassium Tablets |
Angiotensin II (AT1) receptor antagonist.
Losartan Tablets contain Losartan Potassium.
The tablets comply with the requirements stated under Tablets and with the following requirements.
95.0 to 105.0% of the stated amount.
A. Shake a quantity of the powdered tablets containing 0.1 g of Losartan Potassium with 25 mL of acetone for 15 minutes, filter (Whatman GF/C is suitable) and evaporate to dryness under a stream of nitrogen. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of losartan (RS 453).
B. Shake a quantity of the powdered tablets containing 0.2 g of Losartan Potassium with 5 mL of water, filter (Whatman GF/C is suitable) and pass the filtrate through a 0.45-µm membrane filter. 1 mL of the filtrate, yields reaction B characteristic of potassium salts, Appendix VI.
Comply with the requirements in the dissolution test for tablets and capsules, Appendix XII B1.
(a) Use Apparatus 2, rotating the paddle at 75 revolutions per minute.
(b) Use 900 mL of water, at a temperature of 37°, as the medium.
(1) After 30 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 250 nm, Appendix II B using water in the reference cell.
(2) Measure the absorbance of a suitable solution of losartan potassium BPCRS using water in the reference cell.
Calculate the total content of losartan potassium, C22H22ClKN6O, in the medium from the absorbances obtained and using the declared content of C22H22ClKN6O, in losartan potassium BPCRS.
The amount of losartan potassium released after 30 minutes is not less than 70% (Q) of the stated amount.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) To a quantity of the powdered tablets containing 62.5 mg of Losartan Potassium add 125 mL of mobile phase A and mix with the aid of ultrasound for 15 minutes shaking the samples intermittently. Mix for a further 10 minutes with the aid of ultrasound. Add sufficient mobile phase A to produce a solution containing 0.025% w/v of Losartan Potassium.
(2) Dilute 1 volume of solution (1) to 100 volumes and further dilute 1 volume to 10 volumes with mobile phase A.
(3) Dissolve 12 mg of losartan potassium BPCRS in 5 mL of water, add 5 mL of 0.1m hydrochloric acid and heat at 105° for 4 hours. Cool to ambient temperature. Add 5 mL of 0.1m sodium hydroxide and dilute to 50 mL with water. Adjust the pH of the solution to 6.0 with 0.1m hydrochloric acid.
(a) Use a stainless steel column (15 cm × 3.9 mm) packed with octylsilyl silica gel for chromatography (5µm) (Waters Symmetry C8 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 250 nm.
(f) Inject 10 µl of each solution.
Mobile phase A 3 volumes of acetonitrile and 17 volumes of mixed phosphate buffer pH 7.0.
Mobile phase B acetonitrile.
Use the chromatogram obtained with solution (3) to identify the peaks due to impurities L and M. When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to losartan (retention time = about 2.6 minutes) are: impurity M = about 2.4; impurity L = about 2.9.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to impurity L and impurity M is at least 2.0.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity M is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the area of any peak corresponding to impurity L is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the area of any other secondary peak is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of all the secondary peaks is not greater than 10 times the area of the principal peak in the chromatogram obtained with solution (2) (1%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in the mobile phase.
(1) Mix with the aid of ultrasound for 15 minutes a quantity of the powdered tablets containing 25 mg of Losartan Potassium with 30 mL of mobile phase, allow to cool. Add sufficient mobile phase to produce 50 mL and filter through a 0.45-µm PTFE filter.
(2) 0.05% w/v losartan potassium BPCRS.
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5µm) (Prodigy C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 250 nm.
(f) Inject 10 µL of each solution.
3 volumes of acetonitrile and 7 volumes of a solution containing 0.39% w/v sodium dihydrogen orthophosphate and 0.35% v/v triethylamine adjusted to pH 7.0 with orthophosphoric acid.
When the chromatograms are recorded under the prescribed conditions the retention time of Losartan is about 7 minutes.
Calculate the content of C22H22ClKN6O in the tablets using the declared content of C22H22ClKN6O, in losartan potassium BPCRS.
The impurities limited by the requirements of this monograph include impurities L and M listed under Losartan Potassium.
L. [2-butyl-1-[[2′-[1-[[2-butyl-4-chloro-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-imidazol-5-yl]methyl]-1H-tetrazol-5-yl]biphenyl-4-yl]methyl]-4-chloro-1H-imidazol-5-yl]methanol (European Pharmacopoeia Impurity L).
M. [2-butyl-1-[[2′-[2-[[2-butyl-4-chloro-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-imidazol-5-yl]methyl]-2H-tetrazol-5-yl]biphenyl-4-yl]methyl]-4-chloro-1H-imidazol-5-yl]methanol (European Pharmacopoeia Impurity M).