头孢拉定胶囊英国药典BP2013 UpdatedB
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? British Pharmacopoeia Volume III Formulated Preparations: Specific Monographs Cefradine Capsules
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 CHROMATOGRAPHIC CONDITIONS
(a) Use a (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-, 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 μL 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 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 , 80 volumes of 0.2M and
120 volumes of 0.1M .
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 , at a temperature of 37?, as the medium.
PROCEDURE
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 .
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-μm filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with mobile phase A.
(3) 0.012% w/v of each of and in mobile phase A.
(4) 0.003% w/v of (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 (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 (5 μm) (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 μL of each solution.
MOBILE PHASE
Mobile phase A 0.272% w/v of adjusted to pH 3.0 with dilute orthophosphoric acid.
Mobile phase B .
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 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 .
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 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 , 15 volumes of 0.5M , 200 volumes of 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 .
(3) 0.005% w/v of .
(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 (5 μm)
(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 nm.
(f) Inject 5 μL of each solution. MOBILE PHASE
25 volumes of and 75 volumes of .
SYSTEM SUITABILITY
The Assay is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks corresponding to cefradine and cefalexin is at least 4.0.
DETERMINATION OF CONTENT
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 . Calculate the content of C16H17N3O4S (cefalexin) using the declared content of C16H17N3O4S in . 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.