Cefotaxime Injection

Cephalosporin antibacterial.

Cefotaxime Injection is a sterile solution of Cefotaxime Sodium in Water for Injections. It is prepared by dissolving Cefotaxime Sodium for Injection in the requisite amount of Water for Injections before use.

The injection complies with the requirements stated under Parenteral Preparations.

Cefotaxime Injection should be used immediately after preparation but, in any case, within the period recommended by the manufacturer when prepared and stored strictly in accordance with the manufacturer's instructions.

Cefotaxime Sodium for Injection is a sterile material consisting of Cefotaxime Sodium with or without excipients. It is supplied in a sealed container.

The contents of the sealed container comply with the requirements for Powders for Injections or Infusions stated under Parenteral Preparations and with the following requirements.

90.0 to 110.0% of the stated amount.

A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of cefotaxime sodium (RS 044).

B. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Dissolve a quantity of the contents of a sealed container in sufficient of a mixture of equal volumes of methanol and 0.067m mixed phosphate buffer pH 7.0 (solution A) to produce a solution containing the equivalent of 0.4% w/v of cefotaxime.

(2) 0.4% w/v of cefotaxime sodium EPCRS in solution A.

(3) 0.4% w/v of each of cefotaxime sodium EPCRS and cefoxitin sodium BPCRS in solution A.

(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 in air and examine under ultraviolet light (254 nm).

15 volumes of acetone and 85 volumes of a 15.4% w/v solution of ammonium acetate, previously adjusted to pH 6.2 with glacial acetic acid.

The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated principal spots.

The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).

C. Yields reaction A characteristic of sodium salts, Appendix VI.

pH of a solution containing the equivalent of 10.0% w/v of cefotaxime, 4.5 to 6.5, Appendix V L.

A solution containing the equivalent of 10.0% w/v of cefotaxime in carbon dioxide-free water is clear, Appendix IV A. The absorbance of the solution at 430 nm is not greater than 0.60, Appendix II B.

Carry out the method for liquid chromatography, Appendix III D, using the following freshly prepared solutions.

(1) Dissolve a quantity of the contents of a sealed container in sufficient of the mobile phase to produce a solution containing the equivalent of 0.1% w/v of cefotaxime.

(2) 0.001% w/v of cefotaxime acid EPCRS in the mobile phase.

(3) Dilute 1 ml of solution (1) to 10 ml with the mobile phase. To 4 ml of this solution add 1 mL of 2m hydrochloric acid, heat the solution at 40° for 2 hours, add 5 mL of phosphate buffer pH 6.6 and 1 mL of 2m sodium hydroxide and mix.

(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Hypersil 5 µm ODS is suitable).

(b) Use isocratic elution and the mobile phase described below.

(c) Use a flow rate of 1 mL per minute.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 235 nm.

(f) Inject 10 µL of each solution.

(g) For solution (1), allow the chromatography to proceed for at least 8 times the retention time of cefotaxime.

Dissolve 3.5 g of potassium dihydrogen orthophosphate and 11.6 g of disodium hydrogen orthophosphate in 1000 mL of water at pH 7.0 and add 375 mL of methanol.

When the chromatograms are recorded under the prescribed conditions the retention time of cefotaxime is about 6 minutes. If necessary, use another stationary phase or adjust the concentration of methanol in the mobile phase.

The test is not valid unless, in the chromatogram obtained with solution (3), cefotaxime is eluted as the second of the principal peaks and the resolution factor between the two principal peaks is at least 3.5.

In the chromatogram obtained with solution (1):

the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);

the sum of the areas of all the secondary peaks is not greater than 4 times the area of the principal peak in the chromatogram obtained with solution (2) (4%).

When dried in an oven at 100° to 105°, lose not more than 3.0% of their weight. Use 1 g.

Carry out the test for bacterial endotoxins, Appendix XIV C. Dissolve the contents of the sealed container in water BET to give a solution containing the equivalent of 10 mg of cefotaxime per mL (solution A). The endotoxin limit concentration of solution A is 0.5 IU per mL.

Determine the weight of the contents of 10 containers as described in the test for uniformity of weight, Appendix XII C1, Powders for Parenteral Use.

Carry out the method for liquid chromatography, Appendix III D, using the following freshly prepared solutions.

(1) Dissolve a quantity of the mixed contents of the 10 containers in sufficient of the mobile phase to produce a solution containing the equivalent of 0.01% w/v of cefotaxime.

(2) 0.01% w/v of cefotaxime acid EPCRS in the mobile phase.

(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Hypersil 5 µm ODS is suitable).

(b) Use isocratic elution and the mobile phase described below.

(c) Use a flow rate of 1 mL per minute.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 235 nm.

(f) Inject 10 µL of each solution.

Dissolve 3.5 g of potassium dihydrogen orthophosphate and 11.6 g of disodium hydrogen orthophosphate in 1000 mL of water at pH 7.0 and add 375 mL of methanol.

The test is not valid unless the symmetry factor of the principal peak in the chromatogram obtained with solution (2) is less than 2.0.

Calculate the content of C₁₆H₁₇N₅O₇S₂ in a container of average content weight from the declared content of C₁₆H₁₇N₅O₇S₂ in cefotaxime acid EPCRS.

The sealed container should be protected from light.

The label of the sealed container states the quantity of Cefotaxime Sodium contained in it in terms of the equivalent amount of cefotaxime.