Nitrazepam Tablets
Action and use
Benzodiazepine.
Definition
Nitrazepam Tablets contain Nitrazepam.
Content of Nitrazepam, C15H11N3O3
95.0 to 105.0% of the stated amount.
Identification
Shake a quantity of the powdered tablets containing 30 mg of Nitrazepam with 10 mL of acetone, filter and evaporate to dryness. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of nitrazepam (RS 482).
Tests
Carry out the following tests protected from light.
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.
Calculate the total content of nitrazepam, C15H11N3O3, in the medium from the absorbances obtained and using the declared content of C15H11N3O3 in nitrazepam BPCRS.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Mobile phase A0.05m sodium dihydrogen orthophosphate, adjusted to pH 3.0 with orthophosphoric acid.
Mobile phase B20 volumes of mobile phase A and 80 volumes of acetonitrile.
When the chromatograms are recorded under the prescribed conditions the approximate retention time of nitrazepam is about 9 minutes. The retention times relative to nitrazepam are clonazepam, about 1.1; impurity A, about 1.34; impurity B, about 1.58.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to nitrazepam and clonazepam is at least 1.3.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity A is not greater than 0.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the area of any peak corresponding to impurity B is not greater than 0.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
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 all secondary peaks is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.1%).
Uniformity of content
Tablets containing the equivalent of less than 2 mg and/or less than 2% w/w of nitrazepam, comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
35 volumes of acetonitrile and 65 volumes of 0.05m sodium dihydrogen orthophosphate, previously adjusted to pH 3.0 with orthophosphoric acid.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to nitrazepam and clonazepam is at least 1.3.
Calculate the content of C15H11N3O3 in each tablet using the declared content of C15H11N3O3 in nitrazepam BPCRS.
Assay
For tablets containing less than 2 mg and/or less than 2% w/w of Nitrazepam
Use the average of the 10 individual results obtained in the test for Uniformity of content.
For tablets containing 2 mg or more and 2% w/w or more of Nitrazepam
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
The chromatographic conditions described under Uniformity of content may be used.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to nitrazepam and clonazepam is at least 1.3.
Calculate the content of C15H11N3O3 in the tablets using the declared content of C15H11N3O3 in nitrazepam BPCRS.
Storage
Nitrazepam Tablets should be protected from light.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Nitrazepam.