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Cefadroxil monohydrate

EUROPEAN PHARMACOPOEIA 5.0

01/2005:0813 corrected

CEFADROXIL MONOHYDRATE Cefadroxilum monohydricum


C. (6R,7R)-7-[[(2S)-2-amino-2-phenylacetyl]amino]-3-chloro-8oxo-5-thia- 1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid,

C16H17N3O5S,H2O D. (2R,6R,7R)- and (2S,6R,7R)-7-[[(2R)-2-amino2-phenylacetyl]amino]-3-chloro-8-oxo-5-thia1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid (delta-3-cefaclor),

Mr 381.4

DEFINITION (6R,7R)-7-[[(2R)-2-Amino-2-(4-hydroxyphenyl)acetyl]amino]-3methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid monohydrate. Content : 95.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance : white or almost white powder. Solubility : slightly soluble in water, very slightly soluble in alcohol. IDENTIFICATION

E. 2-[[(2R)-2-amino-2-phenylacetyl]amino]-2-(5-chloro-4-oxo-3, Infrared absorption spectrophotometry (2.2.24). 4-dihydro-2H-1,3-thiazin-2-yl)acetic acid, TESTS pH (2.2.3) : 4.0 to 6.0. Suspend 1.0 g in carbon dioxide-free water R and dilute to 20 ml with the same solvent. Specific optical rotation (2.2.7) : + 165 to + 178 (anhydrous substance). Dissolve 0.500 g in water R and dilute to 50.0 ml with the same solvent. Absorbance (2.2.25). Dissolve 20.0 mg in phosphate buffer solution pH 6.0 R and dilute to 100.0 ml with the same solvent. The absorbance of the solution determined at 330 nm is not greater than 0.05. Dilute 10.0 ml of the solution to 100.0 ml with phosphate buffer solution pH 6.0 R. Examined between 235 nm and 340 nm, the diluted solution shows an absorption maximum at 264 nm. The specific absorbance at this maximum is 225 to 250 (anhydrous substance). Related substances. Liquid chromatography (2.2.29). Test solution. Dissolve 50.0 mg of the substance to be examined in mobile phase A and dilute to 50.0 ml with mobile phase A. Reference solution (a). Dissolve 10.0 mg of D--(4-hydroxyphenyl)glycine CRS (impurity A) in mobile phase A and dilute to 10.0 ml with mobile phase A. Reference solution (b). Dissolve 10.0 mg of 7-aminodesacetoxycephalosporanic acid CRS (impurity B) in phosphate buffer solution pH 7.0 R5 and dilute to 10.0 ml with the same buffer solution. Reference solution (c). Dilute 1.0 ml of reference solution (a) and 1.0 ml of reference solution (b) to 100.0 ml with mobile phase A.

F. 3-phenylpyrazin-2-ol.

G. (2R,6R,7R)- and (2S,6R,7R)-7-[[(2R)-2-amino-2phenylacetyl]amino]-3-methylene-8-oxo-5-thia-1azabicyclo[4.2.0]octane-2-carboxylic acid (isocefalexine),

H. (6R,7R)-7-[[(2R)-2-[[(2R)-2-amino-2-phenylacetyl]amino]2-phenylacetyl]amino]-3-chloro-8-oxo-5-thia1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (N-phenylglycyl cefaclor). 1200

See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 5.0

Cefadroxil monohydrate

Reference solution (d). Dissolve 10 mg of dimethylformamide R and 10 mg of dimethylacetamide R in mobile phase A and dilute to 10.0 ml with mobile phase A. Dilute 1.0 ml to 100.0 ml with mobile phase A. Reference solution (e). Dilute 1.0 ml of reference solution (c) to 25.0 ml with mobile phase A. Column : size : l = 0.10 m, = 4.6 mm, stationary phase: spherical octadecylsilyl silica gel for chromatography R (5 m). Mobile phase : mobile phase A : phosphate buffer solution pH 5.0 R, mobile phase B : methanol R2,
Time (min) 0-1 1 - 20 20 - 23 23 - 30 Mobile phase A (per cent V/V) 98 98 70 70 98 98 Mobile phase B (per cent V/V) 2 2 30 30 2 2

Reference solution (a). Dissolve 50.0 mg of cefadroxil CRS in the mobile phase and dilute to 100.0 ml with the mobile phase. Reference solution (b). Dissolve 5 mg of cefadroxil CRS and 50 mg of amoxicillin trihydrate CRS in the mobile phase and dilute to 100 ml with the mobile phase. Column : size : l = 0.25 m, = 4.6 mm, stationary phase : octadecylsilyl silica gel for chromatography R (5 m). Mobile phase : acetonitrile R, a 2.72 g/l solution of potassium dihydrogen phosphate R (4:96 V/V). Flow rate : 1 ml/min. Detection : spectrophotometer at 254 nm. Injection : 20 l. System suitability : reference solution (b) : resolution : minimum 5.0 between the peaks due to cefadroxil and to amoxicillin. Calculate the percentage content of cefadroxil. STORAGE Protected from light. IMPURITIES

Flow rate : 1.5 ml/min. Detection : spectrophotometer at 220 nm. Injection : 20 l ; inject the test solution and reference solutions (c), (d) and (e). Relative retention with reference to cefadroxil (retention time = about 6 min) : dimethylformamide = about 0.4 ; dimethylacetamide = about 0.75. System suitability : resolution : minimum 5.0 between the peaks due to impurity A and to impurity B in the chromatogram obtained with reference solution (c), signal-to-noise ratio : minimum 10 for the second peak in the chromatogram obtained with reference solution (e). Limits : impurity A : not more than the area of the first peak in the chromatogram obtained with reference solution (c) (1.0 per cent), any other impurity : not more than the area of the second peak in the chromatogram obtained with reference solution (c) (1.0 per cent), total: not more than 3 times the area of the second peak in the chromatogram obtained with reference solution (c) (3.0 per cent), disregard limit : 0.05 times the area of the second peak in the chromatogram obtained with reference solution (c) (0.05 per cent) ; disregard the peaks due to dimethylformamide and dimethylacetamide. N,N-Dimethylaniline (2.4.26, Method B) : maximum 20 ppm. Water (2.5.12) : 4.0 per cent to 6.0 per cent, determined on 0.200 g. Sulphated ash (2.4.14) : maximum 0.5 per cent, determined on 1.0 g. ASSAY Liquid chromatography (2.2.29). Test solution. Dissolve 50.0 mg of the substance to be examined in the mobile phase and dilute to 100.0 ml with the mobile phase. General Notices (1) apply to all monographs and other texts

A. (2R)-2-amino-2-(4-hydroxyphenyl)acetic acid,

B. (6R,7R)-7-amino-3-methyl-8-oxo-5-thia-1azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (7-ADCA),

C. (2R,5RS)-2-[(R)-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]carboxymethyl]-5-methyl-5,6-dihydro-2H-1,3-thiazine-4-carboxylic acid,

D. (6R,7R)-7-[[(2S)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (L-cefadroxil), 1201

Cefalexin monohydrate

EUROPEAN PHARMACOPOEIA 5.0

IDENTIFICATION Infrared absorption spectrophotometry (2.2.24). Comparison : cefalexin monohydrate CRS. TESTS pH (2.2.3) : 4.0 to 5.5. E. (6RS)-3-(aminomethylene)-6-(4-hydroxyphenyl)piperazine- Dissolve 50 mg in carbon dioxide-free water R and dilute to 10 ml with the same solvent. 2,5-dione, Specific optical rotation (2.2.7) : + 149 to + 158 (anhydrous substance). Dissolve 0.125 g in phthalate buffer solution pH 4.4 R and dilute to 25.0 ml with the same solvent. Absorbance (2.2.25). Dissolve 50 mg in water R and dilute to 100.0 ml with the same solvent. The absorbance of the solution determined at 330 nm is not greater than 0.05. Dilute 2.0 ml of the solution to 50.0 ml with water R. Examined between 220 nm and 300 nm, the diluted solution F. (6R,7R)-7-[[(2R)-2-[[(2RS)-2-amino-2-(4-hydroxyshows an absorption maximum at 262 nm. The specific phenyl)acetyl]amino]-2-(4-hydroxyphenyl)acetyl]amiabsorbance at this maximum is 220 to 245, calculated with no]-3-methyl-8-oxo-5-thia-1-azabicycreference to the anhydrous substance. lo[4.2.0]oct-2-ene-2-carboxylic acid, Related substances. Liquid chromatography (2.2.29). Test solution. Dissolve 50.0 mg of the substance to be examined in mobile phase A and dilute to 50.0 ml with mobile phase A. Reference solution (a). Dissolve 10.0 mg of D-phenylglycine R in mobile phase A and dilute to G. 3-hydroxy-4-methylthiophen-2(5H)-one, 10.0 ml with mobile phase A. Reference solution (b). Dissolve 10.0 mg of 7-aminodesacetoxycephalosporanic acid CRS in phosphate buffer solution pH 7.0 R5 and dilute to 10.0 ml with mobile phase A. Reference solution (c). Dilute 1.0 ml of reference solution (a) and 1.0 ml of reference solution (b) to 100.0 ml with mobile phase A. H. (6R,7R)-7-[(2,2-dimethylpropanoyl)amino]-3-methyl-8Reference solution (d). Dissolve 10 mg of oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid dimethylformamide R and 10 mg of dimethylacetamide R (7-ADCA pivalamide). in mobile phase A and dilute to 10.0 ml with mobile phase A. Dilute 1.0 ml to 100.0 ml with mobile phase A. 01/2005:0708 Reference solution (e). Dilute 1.0 ml of reference solution (c) to 20.0 ml with mobile phase A. Reference solution (f). Dissolve 10 mg of cefotaxime CEFALEXIN MONOHYDRATE sodium CRS in mobile phase A and dilute to 10.0 ml with mobile phase A. To 1.0 ml of the solution add 1.0 ml of the Cefalexinum monohydricum test solution and dilute to 100 ml with mobile phase A. Column : size : l = 0.10 m, = 4.6 mm, stationary phase : spherical octadecylsilyl silica gel for chromatography R (5 m). Mobile phase : mobile phase A : phosphate buffer solution pH 5.0 R, mobile phase B : methanol R2, C16H17N3O4S,H2O Mr 365.4 DEFINITION (6R,7R)-7-[[(2R)-2-Amino-2-phenylacetyl]amino]-3-methyl8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid monohydrate. Content : 95.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance : white or almost white, crystalline powder. Solubility : sparingly soluble in water, practically insoluble in alcohol. 1202
Time (min) 0-1 1 - 20 20 - 23 23 - 30 Mobile phase A (per cent V/V) 98 98 70 70 98 98 Mobile phase B (per cent V/V) 2 2 30 30 2 2

Flow rate : 1.5 ml/min. Detection : spectrophotometer at 220 nm. Injection : 20 l ; inject the test solution and reference solutions (c), (d), (e) and (f).

See the information section on general monographs (cover pages)

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