Lisinopril Tablets
Action and use
Angiotensin converting enzyme inhibitor.
Definition
Lisinopril Tablets contain Lisinopril Dihydrate.
Content of anhydrous lisinopril, C21H31N3O5
92.5 to 105.0% of the stated amount.
Identification
Equal volumes of glacial acetic acid, butan-1-ol, ethyl acetate and water.
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.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
The chromatographic conditions described under Related substances may be used.
Calculate the total content of lisinopril, C21H31N3O5, in the medium from the chromatograms obtained and using the declared content of C21H31N3O5, in lisinopril dihydrate BPCRS.
The amount of anhydrous lisinopril released is not less than 85% of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in a mixture of 1 volume of methanol and 4 volumes water (solvent A).
200 volumes of acetonitrile R1 and 800 volumes of a 0.408% w/v solution of anhydrous potassium dihydrogen orthophosphate adjusted to pH 2.0 with orthophosphoric acid containing 0.125% w/v of sodium hexanesulfonate.
The test is not valid unless:
in the chromatogram obtained with solution (5), the resolution factor between the peaks due to lisinopril and lisinopril diketopiperazine is at least 5.0;
in the chromatogram obtained with solution (4), the signal to noise ratio of the peak due to lisinopril is at least 10.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to lisinopril diketopiperazine is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.5%);
the area of any other secondary peak is not greater than 0.3 times the area of the principal peak in the chromatogram obtained with solution (3) (0.3%);
the sum of the areas of any other secondary peaks is not greater than 0.6 times the area of the principal peak in the chromatogram obtained with solution (3) (0.6%);
the sum of the content of lisinopril diketopiperazine and the nominal total content of any other impurities is not more than 2%.
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.1%).
Assay
Carry out the method for liquid chromatography, Appendix III D. Using the following solutions in solvent A described under Related Substances.
The chromatographic conditions described under Related substances may be used.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to lisinopril and lisinopril diketopiperazine is at least 5.0.
Calculate the content of C21H31N3O5 in the tablets using the declared content of C21H31N3O5 in lisinopril dihydrate BPCRS.
Labelling
The quantity of active ingredient is stated in terms of the equivalent amount of anhydrous lisinopril.
IMPURITIES
The impurities limited by the requirements of this monograph include:
1. (2S)-2-[(3S,8aS)-3-(4-aminobutyl)-1,4-dioxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-4-phenylbutanoic acid (S,S,S-diketopiperazine) (Lisinopril Dihydrate impurity C),
2. (2S)-2-[(3S,8aR)-3-(4-aminobutyl)-1,4-dioxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-4-phenylbutanoic acid (R,S,S-diketopiperazine) (Lisinopril Dihydrate impurity D).