Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Angiotensin converting enzyme inhibitor.
DEFINITION
Perindopril Erbumine Tablets contain Perindopril Erbumine.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of perindopril erbumine, C19H32N2O5,C4H11N
92.5 to 105.0% of the stated amount.
IDENTIFICATION
A. Dissolve a quantity of the powdered tablets containing 50 mg of Perindopril Erbumine in 10 mL of dichloromethane and centrifuge for 5 minutes. Filter the supernatant liquid (Whatman GF/C is suitable), extract the filtrate with 10 mL of water and wash the upper aqueous layer with two 10-mL quantities of hexane. Evaporate the aqueous layer to dryness on a water bath and dry the residue at 60° at a pressure not exceeding 0.7 kPa, taking care to avoid excessive heating. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the infrared absorption spectrum of perindopril erbumine BPCRS.
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).
TESTS
Dissolution
Comply with the requirements in 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 500 mL of 0.05M hydrochloric acid, at a temperature of 37°, as the medium.
PROCEDURE
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) After 45 minutes withdraw a sample of the medium and filter. Dilute with 0.05M hydrochloric acid, if necessary, to produce a solution expected to contain 0.0004% w/v of Perindopril Erbumine.
(2) 0.0004% w/v of perindopril erbumine BPCRS in 0.05M hydrochloric acid.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (7.5 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (3 µm) (Nucleosil 3 C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 215 nm.
(f) Inject 40 µL of each solution.
MOBILE PHASE
34 volumes of acetonitrile and 66 volumes of water, adjusted to pH 2.0 with a mixture of equal volumes of perchloric acid and water.
DETERMINATION OF CONTENT
Calculate the total content of perindopril erbumine, C19H32N2O5,C4H11N, in the medium from the chromatograms obtained and using the declared content of C19H32N2O5,C4H11N, in perindopril erbumine BPCRS.
LIMITS
The amount of perindopril erbumine 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 in mobile phase A.
(1) To a quantity of the powdered tablets containing 16 mg of Perindopril Erbumine, add 7 mL and mix with the aid of ultrasound. Dilute to 10 mL and filter.
(2) Dilute 1 volume of solution (1) to 200 volumes.
(3) 0.16% w/v of perindopril for peak identification EPCRS.
(4) 0.01% w/v of perindopril impurity standard BPCRS.
(5) Dilute 2 volumes of solution (2) to 10 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.0 mm) packed with spherical octylsilyl silica gel for chromatography (5 µm) (Inertsil C8 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use a column temperature of 60°.
(e) Use a detection wavelength of 215 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
Mobile phase A water adjusted to pH 2.5 with a mixture of equal volumes of perchloric acid and water.
Mobile phase B 0.03% v/v solution of perchloric acid in acetonitrile.
| Time(Minutes) | Mobile phase A(%v/v) | Mobile phase B(%v/v) | Comment |
| 0-(5-t) | 95 | 5 | isocratic |
| (5-t)-(60-t) | 95→40 | 5→60 | linear gradient |
| (60-t)-(65-t) | 40→95 | 60→5 | linear gradient |
Use the chromatogram supplied with perindopril for peak identification EPCRS and the chromatogram obtained with solution (3) to identify the peaks due to impurities B, E, F, H and K. When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to perindopril (retention time = about 25 minutes) are: impurity B = about 0.68; impurity K = about 0.72; impurity E = about 1.2; impurity F = about 1.6; impurity H = about 1.8 (impurity H may be eluted as 1 or 2 peaks).
Use the chromatogram supplied with perindopril impurity standard BPCRS and the chromatogram obtained with solution (4) to identify the peaks due to impurities C and D. When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to perindopril (retention time = about 25 minutes) are: impurity C = about
1.25; impurity D = about 1.3.
The isocratic step is described for a chromatographic system with a dwell volume (D) of 2 mL. If D is different from 2 mL, correct the gradient times with the value t, calculated using the following expression:
SYSTEM SUITABILITY
The test is not valid unless:
the chromatogram obtained with solution (3) closely resembles the chromatogram supplied with perindopril for peak identification EPCRS and the peak-to-valley ratio is at least 3, where Hp is the height above the baseline of the peak due to impurity B and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to impurity K.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity B or F is not greater than 3 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%);
the area of any peak corresponding to impurity C or D is not greater than 1.2 times the area of the principal peak in the chromatogram obtained with solution (2) (0.6%);
the area of any peak corresponding to impurity E is not greater than 0.8 times the area of the principal peak in the chromatogram obtained with solution (2) (0.4%);
the area of any other secondary peak is not greater than half the area of the principal peak in the chromatogram obtained with solution (2) (0.25%);
the sum of the areas of all the secondary peaks excluding any peaks corresponding to impurities B, C, D, E and F is not greater than twice 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 (5) (0.1%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in mobile phase.
(1) To a quantity of the powdered tablets add sufficient of the mobile phase to produce a solution containing 0.004% w/v of Perindopril Erbumine, mix with the aid of ultrasound and filter.
(2) 0.004% w/v of perindopril erbumine BPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used but with an injection volume of 20 µL.
DETERMINATION OF CONTENT
Calculate the content of C19H32N2O5,C4H11N in the tablets using the declared content of C19H32N2O5,C4H11N in perindopril erbumine BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Perindopril Erbumine.
