Enalapril Tablets
Action and use
Angiotensin converting enzyme inhibitor.
Definition
Enalapril Tablets contain Enalapril Maleate.
Content of enalapril maleate, C20H28N2O5,C4H4O4
93.0 to 105.0% of the stated amount.
Identification
15 volumes of glacial acetic acid, 25 volumes of water and 60 volumes of butan-1-ol.
The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).
Tests
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.
Dissolve 2.76 g of sodium phosphate monobasic monohydrate in 1800 mL of water and adjust the pH to 2.2 with orthophosphoric acid. Dilute to 2000 mL with water and mix well (solution A).
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
25 volumes of acetonitrile R1 and 75 volumes of solution A.
Calculate the total content of enalapril maleate, C20H28N2O5,C4H4O4, in the medium from the chromatograms obtained and using the declared content of C20H28N2O5,C4H4O4 in enalapril maleate BPCRS.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Dissolve 2.76 g of sodium phosphate monobasic monohydrate in 1800 mL of water and adjust the pH to 2.2 with orthophosphoric acid. Dilute to 2000 mL with water and mix well (solution A).
The chromatographic conditions described under Dissolution may be used.
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to enalapril (retention time about 5 minutes) are: maleic acid, about 0.2; l-alanyl-l-proline, about 0.3; impurity C, about 0.4; impurity 1, about 0.5 and impurity D, about 1.5.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the principal peak and the peaks due to impurity C or impurity D, is at least 2.0.
Identify any peaks due to impurities C, D, 1 and maleic acid in the chromatogram obtained with solution (1) using the chromatogram obtained with solution (3). Multiply the area of any peak corresponding to impurity C by a correction factor of 0.7 and any peak corresponding to impurity 1 by a correction factor of 0.6.
Identify any peak due to l-alanyl-l-proline in the chromatogram obtained with solution (1) using the chromatogram obtained with solution (4).
In the chromatogram obtained with solution (1):
the area of the peak corresponding to impurity C is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%);
the area of the peak corresponding to impurity D is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%);
the area of any peak corresponding to impurity 1 is not greater than 0.3 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);
the area of any other secondary peak is not greater than 0.2 times the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any other secondary peaks, excluding impurities C, D and 1, is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%);
Disregard any peaks due to maleic acid and l-alanyl-l-proline and 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. Dissolve 2.76 g of sodium phosphate monobasic monohydrate in 1800 mL of water and adjust the pH to 2.2 with orthophosphoric acid. Dilute to 2000 mL with water and mix well (solution A).
The chromatographic conditions described under the Dissolution may be used.
The test is not valid unless, in the chromatogram obtained with solution (2), the symmetry factor is no more than 2.0.
Calculate the content of C20H28N2O5,C4H4O4 in the tablets using the declared content of C20H28N2O5,C4H4O4 in enalapril maleate BPCRS.
Storage
Enalapril Tablets should be protected from light and moisture.
Impurities
The impurities limited by the requirements of this monograph include those listed under Enalapril Maleate and the following: