Cefuroxime Axetil

(Ph Eur monograph 1300)

 

C20H22N4O10S   510.5      64544-07-6

 

Ph Eur


 

 

DEFINITION

 

Cefuroxime axetil contains not less than 96.0 per cent and not more than the equivalent of 102.0 per cent of a mixture of the 2 diastereoisomers of (1RS)-1-(acetyloxy)ethyl (6R,7R)-3-[(carbamoyloxy)methyl]-7-[[(Z)-2-(furan-2-yl)-2-(methoxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, calculated with reference to the anhydrous and acetone-free substance.

 

CHARACTERS

 

A white or almost white powder, slightly soluble in water, soluble in acetone, in ethyl acetate and in methanol, slightly soluble in alcohol.

 

IDENTIFICATION

 

A.    Examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum obtained with cefuroxime axetil CRS.

 

B.    Examine the chromatograms obtained in the Assay. The retention time and size of the principal peaks in the chromatogram obtained with the test solution are the same as those of the peaks due to diastereoisomers A and B of cefuroxime axetil in the chromatogram obtained with reference solution (d).

 

TESTS

 

Diastereoisomer ratio

 

Examine by liquid chromatography (2.2.29) as described under Assay. In the chromatogram obtained with the test solution, the ratio of the peak due to cefuroxime axetil diastereoisomer A to the sum of the peaks due to cefuroxime axetil diastereoisomers A and B is between 0.48 and 0.55 by the normalisation procedure.

 

Related substances

 

Examine by liquid chromatography (2.2.29) as described under Assay. Calculate the percentage content of related substances from the areas of the peaks in the chromatogram obtained with the test solution by the normalisation procedure, disregarding any peak with an area less than 0.05 times that of the 2 principal peaks in the chromatogram obtained with reference solution (a). The percentage sum of the pair of peaks corresponding to the E-isomers located by comparison with the chromatogram obtained with reference solution (c) is not greater than 1.0 per cent, the percentage sum of the pair of peaks corresponding to the D3-isomers located by comparison with the chromatogram obtained with reference solution (b) is not greater than 1.5 per cent and the area of any other secondary peak is not greater than 0.5 per cent. The sum of related substances is not greater than 3.0 per cent.

 

Acetone (2.4.24)

 

Not more than 1.1 per cent.

 

Water (2.5.12)

 

Not more than 1.5 per cent, determined on 0.400 g by the semi-micro determination of water.

 

ASSAY

 

Examine by liquid chromatography (2.2.29).

 

Test solution

 

Prepare the solution immediately before use. Dissolve 10.0 mg of the substance to be examined in the mobile phase and dilute to 50.0 ml with the mobile phase.

 

Reference solution (a)

 

Dilute 1.0 ml of the test solution to 100.0 ml with the mobile phase.

 

Reference solution (b)

 

Heat 5 ml of the test solution at 60 C for 1 h to generate the D3-isomers.

 

Reference solution (c)

 

Expose 5 ml of the test solution to ultraviolet light at 254 nm for 24 h to generate E-isomers.

 

Reference solution (d)

 

Prepare the solution immediately before use. Dissolve 10.0 mg of cefuroxime axetil CRS in the mobile phase and dilute to 50.0 ml with the mobile phase.

 

The chromatographic procedure may be carried out using:

 

a column 0.25 m long and 4.6 mm in internal diameter packed with trimethylsilyl silica gel for chromatography R (5 mm),

 

as mobile phase at a flow rate of 1.0 ml/min a mixture of 38 volumes of methanol  R and 62 volumes of a 23 g/l solution of ammonium dihydrogen phosphate R,

 

as detector a spectrophotometer set at 278 nm.

 

Inject 20 ml each of reference solutions (a), (b), (c) and (d). When the chromatograms are recorded in the prescribed conditions the retention times relative to cefuroxime axetil diastereoisomer A (second peak) are approximately 0.9 for cefuroxime axetil diastereoisomer B, 1.2 for the cefuroxime axetil D3-isomers and 1.7 and 2.1 for the E-isomers. The test is not valid unless in the chromatogram obtained with reference solution (d), the resolution between the peaks corresponding to cefuroxime axetil diastereoisomers A and B is at least 1.5. In the chromatogram obtained with reference solution (b), the resolution between the peaks corresponding to cefuroxime axetil diastereoisomer A and cefuroxime axetil D3-isomer is at least 1.5.

 

Inject reference solution (d) solution 6 times. The assay is not valid unless the relative standard deviation of the sum of the peaks corresponding to cefuroxime axetil diastereoisomers A and B is at most 2.0 per cent.

 

Calculate the percentage content of C20H22N4O10S from the sum of areas of the two diastereoisomer peaks and the declared content of C20H22N4O10S in cefuroxime axetil CRS.

 

STORAGE

 

Store in an airtight container , protected from light.

 

IMPURITIES

 

A.    1-(acetyloxy)ethyl (6R,7R)-3-[(carbamoyloxy)methyl]-7-[[(Z)-2-(furan-2-yl)-2-(methoxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate (D3-isomers),

 

B.    (1RS)-1-(acetyloxy)ethyl (6R,7R)-3-[(carbamoyloxy)methyl]-7-[[(E)-2-(furan-2-yl)-2-(methoxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate (E-isomers),

 

C.    R = CO-CCl3: (6R,7R)-7-[[(Z)-2-(furan-2-yl)-2-(methoxyimino)acetyl]amino]-8-oxo-3-[[[(trichloroacetyl)carbamoyl]oxy]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid,

 

D.    R = H: cefuroxime.

 

 

 


Ph Eur

 

Action and use

 

Antibacterial.

 

Preparation

 

Cefuroxime Axetil Tablets