头孢拉定胶囊英国药典BP2013 UpdatedB.doc

British Pharmacopoeia Volume III Formulated Preparations Specific Monographs Cefradine Capsules General Notices Action and use Cephalosporin antibacterial DEFINITION Cefradine Capsules contain Cefradine The capsules comply with the requirements stated under Capsules and with the following requirements 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 A The infrared absorption spectrum of the contents of the capsules Appendix II A is concordant with the reference spectrum of cefradine RS 050 If the spectra are not concordant dissolve a quantity of the capsule contents containing 30 mg of Cefradine in 10 mL of methanol evaporate to dryness at 40 at a pressure of 2 kPa and prepare a new spectrum B Carry out the method for thin layer chromatography Appendix III A using the following solutions 1 Shake a quantity of the contents of the capsules containing 0 1 g of Cefradine with 25 mL of 0 01M ammonia for 45 minutes and dilute 1 mL of the resulting solution to 10 mL with 0 01M ammonia 2 0 040 w v of cefradine BPCRS in 0 01M ammonia CHROMATOGRAPHIC CONDITIONS a Use a TLC silica gel plate Analtech plates are suitable Impregnate the plate by placing it in a tank containing a shallow layer of a 5 v v solution of n tetradecane in n hexane allowing the impregnating solvent to ascend to the top removing the plate from the tank and allowing the solvent to evaporate use with the flow of the mobile phase in the same direction that the impregnation was carried out b Use the mobile phase as described below c Apply 5 L of each solution d Develop the plate to 15 cm e After removal of the plate heat at 90 for 2 to 3 minutes and spray the hot plate with a 0 1 w v solution of ninhydrin in the mobile phase Heat at 90 for 15 minutes in a circulating air oven with the plates parallel to the airflow cool for 15 minutes protected from light and examine in daylight MOBILE PHASE 3 volume of acetone 80 volumes of 0 2M anhydrous disodium hydrogen orthophosphate and 120 volumes of 0 1M citric acid CONFIRMATION 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 TEST CONDITIONS a Use Apparatus 1 rotating the basket at 100 revolutions per minute b Use 900 mL of 0 12M hydrochloric acid at a temperature of 37 as the medium PROCEDURE 1 After 45 minutes withdraw a 10 mL sample of the medium filter and dilute the filtered solution if necessary with sufficient 0 12M hydrochloric acid to produce a solution expected to contain about 0 0025 w v of Cefradine Measure the absorbance of the filtered sample at the maximum at 255 nm Appendix II B using 0 12M hydrochloric acid in the reference cell 2 Measure the absorbance of a 0 0025 w v solution of cefradine BPCRS in 0 12M hydrochloric acid using 0 12M hydrochloric acid in the reference cell DETERMINATION OF CONTENT 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 1 Shake a quantity of the contents of the capsules containing 0 3 g of Cefradine in mobile phase A add sufficient mobile phase A to produce 50 mL and filter through a 0 45 m filter 2 Dilute 1 volume of solution 1 to 100 volumes with mobile phase A 3 0 012 w v of each of cefradine BPCRS and cefalexin BPCRS in mobile phase A 4 0 003 w v of cyclohexa 1 4 dienylglycine EPCRS impurity B in mobile phase A 5 Dissolve 6 mg of cefradine for peak identification EPCRS containing impurities C D and E in 1 mL of mobile phase A 6 Dissolve the contents of a vial of cefradine impurity mixture EPCRS containing impurities A and G in 1 mL of mobile phase A CHROMATOGRAPHIC CONDITIONS a Use a stainless steel column 15 cm 4 6 mm packed with octadecylsilyl silica gel for chromatography 5 m Varian Chrompack Inertsil ODS 3 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 30 e Use a detection wavelength of 220 nm f Inject 25 L of each solution MOBILE PHASE Mobile phase A 0 272 w v of potassium dihydrogen orthophosphate adjusted to pH 3 0 with dilute orthophosphoric acid Mobile phase B methanol R2 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 SYSTEM SUITABILITY 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 LIMITS 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 In the chromatogram obtained with solution 1 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 4 0 25 the area of any peak corresponding to impurity A 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 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 1 Dissolve a quantity of the powdered mixed contents of 20 capsules to produce a solution containing 0 05 w v of Cefradine 2 0 05 w v of cefradine BPCRS 3 0 005 w v of cefalexin BPCRS 4 Dilute 1 volume of solution 2 to 10 volumes with solution A Mix equal volumes of this solution and solution 3 CHROMATOGRAPHIC CONDITIONS a Use a stainless steel column 10 cm 4 6 mm packed with octadecylsilyl silica gel for chromatography 5 m Hypersil ODS is suitable b Use isocratic elution and the mobile phase described below c Use a flow rate of 1 5 mL per minute d Use an ambient column temperature e Use a detection wavelength of 254