5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid,3-(acetyloxy)methyl-7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo,monosodium salt,[6R-[6a,7b(Z)]]-.
Sodium (6R,7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 72-(Z)-(O-methyloxime),acetate (ester) [64485-93-4].
»Cefotaxime Sodium contains the equivalent of not less than 916µg and not more than 964µg of cefotaxime (C16H17N5O7S2)per mg,calculated on the dried basis.
Packaging and storage Preserve in tight containers.
Labeling Where it is intended for use in preparing injectable dosage forms,the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.
Clarity and color of solution Transfer 2.5g of it to a 25-mLvolumetric flask.Dissolve in and dilute with carbon dioxide-free water to volume,mix,and examine immediately:the solution is clear.Measure the absorbance of this solution at 430nm in a 1-cm cell,using carbon dioxide-free water as the blank:its absorbance is not more than 0.20.Transfer 10mLof the solution to a glass test tube,add 1mLof glacial acetic acid,mix,and examine immediately:the solution is clear.
A: Infrared Absorption á197Kñ.
B: The chromatogram of the Assay obtained as directed in the Assayexhibits a major peak for cefotaxime,the retention time of which corresponds to that exhibited in the chromatogram of the Standard preparationobtained as directed in the Assay.
C: It responds to the tests for Sodium á191ñ.
Specific rotation á781Sñ: between +58and +64.
Test solution: 10mg per mL,in water.
pHá791ñ: between 4.5and 6.5,in a solution (1in 10).
Loss on drying á731ñ Dry it at 100to 105for 3hours:it loses not more than 3.0%of its weight.
Chromatographic purity Using the chromatogram of the Assay preparationobtained in the Assay,calculate the percentage of each impurity by the formula:
100ri/(ris+rc),in which riis the peak area response of a given impurity,risis the sum of all of the impurity peak area responses,and rcis the peak area response for the main cefotaxime peak.[NOTEDisregard any impurity peak that is less than 0.1%.]Not more than 1.0%of any individual impurity is found,and the sum of all impurities found is not more than 3.0%.
Other requirements Where the label states that Cefotaxime Sodium is sterile,it meets the requirements for Sterility á71ñwhen tested as directed for Membrane Filtrationunder Test for Sterility of the Product to be Examined,and for Bacterial endotoxinsunder Cefotaxime for Injection.Where the label states that Cefotaxime Sodium must be subjected to further processing during the preparation of injectable dosage forms,it meets the requirements for Bacterial endotoxinsunder Cefotaxime for Injection.
0.05M Phosphate buffer Dissolve 7.1g of anhydrous dibasic sodium phosphate in 1000mLof water,and adjust with phosphoric acid to a pHof 6.25.
Solution A Prepare a mixture of 0.05M Phosphate bufferand methanol (86:14).Filter through a filter having a porosity of 0.5µm or less,and degas before use.
Solution B Prepare a mixture of 0.05M Phosphate bufferand methanol (60:40).Filter through a filter having a porosity of 0.5µm or less,and degas before use.
Mobile phase Use variable mixtures of Solution Aand Solution Bas directed for Chromatographic system.
Standard preparation Transfer about 40mg of USP Cefotaxime Sodium RS,accurately weighed,to a 50-mLvolumetric flask,add about 40mLof Solution A,swirl to dissolve,dilute with Solution Ato volume,and mix.[NOTEUse this solution promptly.It may be used within 24hours if stored in the refrigerator.]
Sensitivity solution Transfer 2.0mLof Standard preparation to a 100-mLvolumetric flask,dilute with Solution Ato volume,and mix.Transfer 2.0mLof this solution to a 20-mLvolumetric flask,dilute with Solution Ato volume,and mix.
Resolution solution Mix 1mLof Standard preparation,7.0mLof water,and 2.0mLof methanol.Add 25mg of sodium carbonate,mix,and allow to stand at room temperature for 10minutes,with occasional swirling.Add 3drops of glacial acetic acid and 1mLof Standard preparation,and mix.
Assay preparation Transfer about 40mg of Cefotaxime Sodium,accurately weighed,to a 50-mLvolumetric flask,add Solution Ato dissolve it,dilute with Solution Ato volume,and mix.[NOTEUse this solution promptly.It may be used within 24hours if stored in a refrigerator.]
Chromatographic system (see Chromatography á621ñ)The liquid chromatograph is equipped with a 235-nm detector and a 3.9-mm ×15-cm column that contains 5-µm packing L1and is maintained at a constant temperature of about 30.The flow rate is about 1mLper minute.The system is equilibrated with 100%Solution A.Seven minutes after injection of the solution under test,the proportion of Solution Bis increased linearly from 0%to 20%at a rate of 10%per minute and is maintained at that composition for 7minutes.The proportion of Solution Bis then increased linearly at a rate of 2.7%per minute until the proportion of Solution Bis 100%,and is held at that composition for 5minutes,after which the proportion of Solution Ais increased linearly to 100%at a rate of 20%per minute.Chromatograph the Resolution solution,and record the peak responses as directed under Procedure:the retention times are about 3.5minutes for desacetylcefotaxime and 14minutes for cefotaxime,and the resolution,R,between the two peaks is not less than 20.Chromatograph the Standard preparation,and record the peak responses as directed under Procedure:the retention time for the main cefotaxime peak is between 12and 15minutes,the tailing factor is not more than 2,and the relative standard deviation for replicate injections is not more than 1.5%.Chromatograph the Sensitivity solution,and record the peak responses as directed under Procedure:the response of the cefotaxime peak is between 0.18%and 0.22%of the response of the cefotaxime peak in the chromatogram obtained from the Standard preparation.
Procedure Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparation into the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity,in µg per mg,of cefotaxime (C16H17N5O7S2)in the portion of Cefotaxime Sodium taken by the formula:
50(CP/W)(rU/rS),in which Cis the concentration,in mg per mL,of USP Cefotaxime Sodium RSin the Standard preparation,Pis the designated content,in µg per mg,of cefotaxime (C16H17N5O7S2)in USP Cefotaxime Sodium RS,Wis the weight,in mg,of Cefotaxime Sodium taken to prepare the Assay preparation,and rUand rSare the cefotaxime peak area responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information Staff Liaison:William W.Wright,Ph.D.,Scientific Fellow
Expert Committee:(PA7)Pharmaceutical Analysis 7