Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Angiotensin II (AT1) receptor antagonist.
DEFINITION
Telmisartan Tablets contain Telmisartan.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of telmisartan, C33H30N4O2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of powdered tablets containing 80 mg of Telmisartan with 15 mL of water, filter and discard the filtrate. Extract the residue from the filter with 15 mL of dichloromethane in a flask and with the aid of ultrasound. Transfer this solution to a separating funnel, add 15 mL of water and shake. Separate the dichloromethane layer and evaporate to dryness under a stream of nitrogen. To the residue, add 10 mL of acetonitrile and filter. Evaporate the filtrate to dryness under a stream of nitrogen and dry the residue at 105° for 1 hour. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of telmisartan (RS 486).
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 75 revolutions per minute.
(b) Use 900 mL of a pH 7.5 phosphate buffer solution, prepared by dissolving 13.61 g of potassium dihydrogen orthophosphate in 800 mL of water, adjusted to pH 7.5 using 2M sodium hydroxide and diluted to 1000 mL, at a temperature of 37°, as the medium.
PROCEDURE
(1) After 45 minutes withdraw a 10-mL sample of the medium and measure the absorbance of the filtered sample, diluted with the dissolution medium, if necessary, to produce a solution expected to contain 0.001% w/v of Telmisartan, at the maximum at 296 nm, Appendix II B using dissolution medium in the reference cell.
(2) To about 40 mg of telmisartan BPCRS add 1 mL of 0.1M sodium hydroxide and sufficient methanol to produce a solution containing 0.04% w/v of Telmisartan. Dilute 1 volume of this solution to 40 volumes with the dissolution medium. Measure the absorbance of this solution using dissolution medium in the reference cell.
DETERMINATION OF CONTENT
Calculate the total content of telmisartan, C33H30N4O2, in the medium from the absorbances obtained and using the declared content of C33H30N4O2 in telmisartan BPCRS.
LIMITS
The amount of telmisartan 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) Dissolve a quantity of the powdered tablets containing 25 mg of Telmisartan in 5 mL of methanol and 100 µL of a 4% w/v solution of sodium hydroxide and mix with the aid of ultrasound. Add sufficient methanol to produce a solution containing 0.05% w/v of Telmisartan.
(2) Dilute 1 volume of solution (1) to 10 volumes with methanol. Dilute 1 volume of this solution to 100 volumes with methanol.
(3) Dissolve the contents of a vial of telmisartan for system suitability EPCRS in 2 mL of methanol.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4.0 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Kromasil C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 230 nm.
(f) Inject 10 µL of each solution.
MOBILE PHASE
Mobile phase A Dissolve 2.0 g of potassium dihydrogen orthophosphate and 3.8 g of sodium pentanesulfonate monohydrate in 950 mL water, adjust to pH 3.0 with dilute orthophosphoric acid and dilute to 1000 mL with water.
Mobile phase B 20 volumes of methanol and 80 volumes of acetonitrile.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-3 | 70 | 30 | isocratic |
| 3-28 | 70→20 | 30→80 | linear gradient |
| 28-30 | 20→70 | 80→30 | linear gradient |
| 30-35 | 70 | 30 | re-equilibration |
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to telmisartan (retention time about 15 minutes) are: impurity A, about 0.2; impurity E, about 0.6; impurity F, about 0.7; impurity B, about 0.9; impurity C, about 1.5.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) is similar to the chromatogram supplied with telmisartan for system suitability EPCRS and the resolution between the peaks due to impurity B and telmisartan is at least 3.0.
LIMITS
Use the chromatogram supplied with telmisartan for system suitability EPCRS and the chromatogram obtained with solution (3) to identify the peaks due to impurities A, B, C, E and F.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity C is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the area of any peak corresponding to impurity A or B is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.15% of each);
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) (1.0%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dissolve a quantity of the powdered tablets containing 25 mg of Telmisartan in 5 mL of methanol and 100 µL of a 4% w/v solution of sodium hydroxide. Mix with the aid of ultrasound, dilute to 50 mL with methanol and filter. To the filtrate, add sufficient methanol to produce a solution containing 0.0005% w/v of Telmisartan.
(2) 0.0005% w/v of telmisartan BPCRS in methanol.
(3) Dissolve the contents of a vial of telmisartan for system suitability EPCRS in 2 mL of methanol.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) is similar to the chromatogram supplied with telmisartan for system suitability EPCRS and the resolution between the peaks due to impurity B and telmisartan is at least 3.0.
DETERMINATION OF CONTENT
Calculate the content of C33H30N4O2 in the tablets using the declared content of C33H30N4O2 in telmisartan BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A, B, C, E and F listed under Telmisartan.
