BP 2025 (Ph. Eur. 11.6 update)
Action and use
Cephalosporin antibacterial.
DEFINITION
Cefalexin Oral Suspension is a suspension of Cefalexin Monohydrate in a suitable flavoured vehicle. It is prepared by dispersing the dry ingredients in the specified volume of Water just before issue for use.
The dry ingredients comply with the requirements for Powders and Granules for Oral Solutions and Oral Suspensions stated under Oral Liquids.
Content of anhydrous cefalexin, C16H17N3O4S
When freshly constituted, not more than 120.0% of the stated amount. When stored at the temperature and for the period stated on the label during which the Oral Suspension may be expected to be satisfactory for use, not less than 80.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Shake a quantity of the oral suspension containing the equivalent of 0.2 g of anhydrous cefalexin with 70 mL of methanol, filter, evaporate to dryness and dissolve the residue in sufficient 0.5M hydrochloric acid to produce 50 mL.
(2) 0.4% w/v of cefalexin BPCRS in a mixture of equal volumes of methanol and 0.067M mixed phosphate buffer pH 7.0.
(3) 0.4% w/v of each of cefalexin BPCRS and cefradine BPCRS in a mixture of equal volumes of methanol and 0.067M mixed phosphate buffer pH 7.0.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silanised silica gel HF254.
(b) Use the mobile phase as described below.
(c) Apply 1 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry and examine under ultraviolet light (254 nm).
MOBILE PHASE
15 volumes of acetone and 85 volumes of a 15.4% w/v solution of ammonium acetate, previously adjusted to pH 6.2 with 5M acetic acid.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) is similar in position and size to that in the chromatogram obtained with solution (2).
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the peak in the chromatogram obtained with solution (2).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in mobile phase A.
(1) Shake a quantity of the oral suspension containing 0.1g of anhydrous cefalexin with 50 mL of water for 30 minutes, dilute to 100 mL using mobile phase A and filter.
(2) Mix 1 volume of a solution containing 0.1% w/v 7-aminodesacetoxycephalosporanic acid BPCRS (impurity B) in solution A, with 1 volume of a solution containing 0.1% w/v D-phenylglycine (impurity A) in mobile phase A. Dilute to 100 volumes.
(3) 0.001% w/v each of dimethylformamide and dimethylacetamide.
(4) Mix 1 volume of solution (1) with 1 volume of a solution containing 0.1% w/v cefotaxime sodium EPCRS in mobile phase A and dilute to 100 volumes.
(5) Dilute 1 volume of solution (2) to 10 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with spherical octadecylsilyl silica gel for chromatography (5μm) (ACE 5 C18 is suitable).
(b) Use gradient 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 220 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
Mobile phase A phosphate buffer solution pH 5.0.
Mobile phase B methanol R2.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-1 | 98 | 2 | isocratic |
| 1-20 | 98→70 | 2→30 | linear gradient |
| 20-23 | 70 | 30 | isocratic |
| 23-24 | 70→98 | 30→2 | linear gradient |
| 24-30 | 98 | 2 | re-equilibration |
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to cefalexin (retention time about 12 minutes) are: impurity A, about 0.10; impurity B, about 0.13; cefotaxime, about 1.1.
SYSTEM SUITABILITY
The test is not valid unless:
in the chromatogram obtained with solution (2), the resolution between the peaks due to impurity A and impurity B is at least 2.0 and;
in the chromatogram obtained with solution (4), the resolution between the peaks due to cefalexin and cefotaxime is at least 1.5.
LIMITS
Identify any peak due to dimethylformamide and dimethylacetamide in the chromatogram obtained with solution (1) using the chromatogram obtained with solution (3).
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity B is not greater than the area of the peak due to impurity B in the chromatogram obtained with solution (2) (1%);
the area of any other secondary peak is not greater than the area of the peak due to impurity A in the chromatogram obtained with solution (2) (1%);
the sum of the areas of any secondary peaks is not greater than 3 times the area of the peak due to impurity A in the chromatogram obtained with solution (2) (3%).
Disregard any peaks due to dimethylformamide and dimethylacetamide and any peaks with an area less than the area of the peak due to impurity A in the chromatogram obtained with solution (5) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a weighed quantity of the oral suspension containing the equivalent of 0.25 g of anhydrous cefalexin with 100 mL of water for 30 minutes. Add sufficient water to produce 500 mL and filter.
(2) 0.05% w/v of cefalexin BPCRS.
(3) 0.01% w/v of each of cefalexin BPCRS and cefradine BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 μm) (Nucleosil C18 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 20 μL of each solution.
MOBILE PHASE
2 volumes of methanol, 5 volumes of acetonitrile, 10 volumes of a 1.36% w/v solution of potassium dihydrogen orthophosphate and 83 volumes of water.
SYSTEM SUITABILITY
The Assay is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks corresponding to cefalexin and cefradine is at least 4.0.
Inject solution (2) six times. The Assay is not valid unless the relative standard deviation of the area of the principal peak is at most 1.0%.
DETERMINATION OF CONTENT
Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C16H17N3O4S, weight in volume, using the declared content of C16H17N3O4S in cefalexin BPCRS.
Repeat the procedure using a portion of the oral suspension that has been stored at the temperature and for the period stated on the label during which it may be expected to be satisfactory for use.
STORAGE
The Oral Suspension should be stored at the temperature and used within the period stated on the label.
LABELLING
The quantity of active ingredient is stated in terms of the equivalent amount of anhydrous cefalexin.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Cefalexin Monohydrate.
