Cefradine Capsules
Action and use
Cephalosporin antibacterial.
Definition
Cefradine Capsules contain Cefradine.
Content of cephalosporins, calculated as the sum of cefradine (C16H19N3O4S), cefalexin (C16H17N3O4S) and 4′,5′-dihydrocefradine (C16H21N3O4S)
90.0 to 105.0% of the stated amount of Cefradine.
Identification
3 volume of acetone, 80 volumes of 0.2m anhydrous disodium hydrogen orthophosphate and 120 volumes of 0.1m citric acid.
The principal spot in the chromatogram obtained with solution (1) corresponds 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.
Calculate the total content of cephalosporins, as the sum of the contents of C16H19N3O4S, C16H17N3O4S and C16H21N3O4S in the medium from the absorbance obtained and using the declared content of total cephalosporins in cefradine BPCRS.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
When the chromatograms are recorded under the prescribed conditions the retention times relative to Cefradine (retention time = about 15 minutes) are: impurity A = about 0.27; impurity B = about 0.32; impurity C = about 0.53; impurity D = about 0.63; impurity E = about 0.80; impurity F = about 0.92; cefalexin = about 0.95; 4′,5′-dihydrocefradine = about 1.06; impurity G = about 1.32.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to cefalexin and cefradine is at least 4.0.
Identify any peaks in the chromatogram obtained with solution (1) due to impurities C, D and E using the chromatogram obtained with solution (5) and the chromatogram supplied with cefradine for peak identification EPCRS. Identify any peaks in the chromatogram obtained with solution (1) due to impurities A and G using the chromatogram obtained with solution (6) and the chromatogram supplied with cefradine impurity mixture EPCRS. Identify any peak in the chromatogram obtained with solution (1) due to impurity B using the chromatogram obtained with solution (4). Multiply the area of any peak corresponding to impurity B by the following correction factor: 3.4.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity A, B, D, F or G is not greater than 0.25 times the area of the principal peak in the chromatogram obtained with solution (2) (0.25% for each);
the area of any peak corresponding to impurity C 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 E is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);
the area of any other secondary peak is not greater than 0.25 times 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 is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (2%).
Disregard the peaks due to cefalexin, and 4′,5′-dihydrocefradine and any peak with an area less than 0.05 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).
Cefalexin
Not more than 10.0%, calculated as the percentage of C16H17N3O4S in the sum of C16H19N3O4S, C16H17N3O4S and C16H21N3O4S determined in the Assay.
4′,5′-Dihydrocefradine
Not more than 2.0%, calculated as the percentage of C16H21N3O4S in the sum of C16H19N3O4S, C16H17N3O4S and C16H21N3O4S determined in the Assay.
Loss on drying
The contents of the capsules, when dried at 60° at a pressure not exceeding 0.7 kPa for 3 hours, lose not more than 7.0% of their weight. Use 1 g.
Assay
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in a mixture of 3 volumes of 0.7m glacial acetic acid, 15 volumes of 0.5m sodium acetate, 200 volumes of methanol and 782 volumes of water (solution A).
25 volumes of methanol and 75 volumes of phosphate buffer solution pH 5.0.
When the chromatograms are recorded under the prescribed conditions, the retention time of the peak due to 4’,5’-dihydrocefradine relative to that of cefradine is about 1.6.
The Assay is not valid unless, in the chromatogram obtained with solution (4), the resolution factor between the peaks corresponding to cefradine and cefalexin is at least 4.0.
Calculate the content of cephalosporins in the capsules by determining the sum of the contents of C16H19N3O4S, C16H17N3O4S and C16H21N3O4S. Calculate the content of C16H19N3O4S (cefradine) using the declared content of C16H19N3O4S in cefradine BPCRS. Calculate the content of C16H17N3O4S (cefalexin) using the declared content of C16H17N3O4S in cefalexin BPCRS. Calculate the content of C16H21N3O4S (4′,5′-dihydrocefradine) using the declared content of C16H17N3O4S in cefalexin BPCRS and multiplying the area of the peak due to 4′,5′-dihydrocefradine by a correction factor of 1.6.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Cefradine.