Action and use
Angiotensin II (AT1) receptor antagonist.
DEFINITION
Valsartan Tablets contain Valsartan.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of valsartan, C24H29N5O3
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Shake a quantity of the powdered tablets containing 50 mg of Valsartan with 20 mL of dichloromethane for 10 minutes, 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 residue, Appendix II A, is concordant with the reference spectrum of Valsartan (RS 473). Disregard any bands occurring between 1250 and 1325 cm-1 .
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the principal peak in the chromatogram obtained with solution (2).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute
(b) Use 900 mL of phosphate buffer pH 6.8, at a temperature of 37°, as the medium.
PROCEDURE
(1) After 30 minutes withdraw a 10 mL sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium to give a solution expected to contain 0.004% w/v of Valsartan, at the maximum at 250 nm, Appendix II B, using phosphate buffer pH 6.8 in the reference cell.
(2) Measure the absorbance of a 0.004% w/v solution of valsartan BPCRS in phosphate buffer pH 6.8 at the maximum at 250 nm, Appendix II B, using phosphate buffer pH 6.8 in the reference cell.
DETERMINATION OF CONTENT
Calculate the total content of valsartan, C24H29N5O3, in the medium from the absorbances obtained and using the declared content of C24H29N5O3, in valsartan BPCRS.
LIMITS
The amount of valsartan released is not less than 80% (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 50 mg of Valsartan with 80 mL of the mobile phase with the aid of ultrasound, add sufficient mobile phase to produce 100 mL and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase. Dilute 1 volume of the resulting solution to 10 volumes with the mobile phase.
(3) Dissolve the contents of a vial of valsartan for system suitability EPCRS (containing impurity C) in 1.0 mL on the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 3.0 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 μm) (Nucelosil-100 C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 0.4 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 225 nm.
(f) Inject 10 μL of each solution.
(g) Allow the chromatography to proceed for 6 times the retention time of valsartan.
MOBILE PHASE
1 volume of glacial acetic acid, 500 volumes of acetonitrile R1 and 500 volumes of water.
When the chromatograms are recorded under the prescribed conditions, the relative retention with reference to valsartan (retention time, about 5 minutes) is: impurity C, about 0.8.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to impurity C and valsartan is at least 3.0.
LIMITS
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 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 secondary peaks is not greater than 7 times the area of the principal peak in the chromatogram obtained with solution (2) (0.7%).
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) To a quantity of the powdered tablets containing 50 mg of Valsartan, add 80 mL of the mobile phase and mix with the aid of ultrasound. Add sufficient mobile phase to produce 100 mL and filter. Dilute 1 volume of this solution to 10 volumes with the mobile phase.
(2) 0.005% w/v of valsartan BPCRS in the mobile phase.
(3) Dissolve the contents of a vial of valsartan for system suitability EPCRS (containing impurity C) in 1.0 mL of 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 impurity C and valsartan is at least 3.0.
DETERMINATION OF CONTENT
Calculate the content of C24H29N5O3 in the tablets using the declared content of C24H29N5O3 in valsartan BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Valsartan.
