(6R,7R)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid,72-(Z)-[O-(carboxymethyl)oxime]trihydrate [79350-37-1].
»Cefixime contains the equivalent of not less than 950µg and not more than 1030µg of Cefixime (C16H15N5O7S2)per mg,calculated on the anhydrous basis.
Packaging and storage Preserve in tight containers.
Labeling Label to indicate that it is the trihydrate form.Where the quantity of Cefixime is indicated in the labeling of any preparation containing Cefixime,this shall be understood to be in terms of anhydrous cefixime (C16H15N5O7S2).
Identification,Infrared Absorption á197Kñ Prepare the test specimen as follows.Dissolve about 5mg of it by trituration in 2mLof methanol and evaporate with the aid of gentle heat to dryness.
Specific rotation á781Sñ: between -75and -88.
Test solution: 10mg per mL,in sodium bicarbonate solution (2in 100).
Crystallinity á695ñ: meets the requirements.
pHá791ñ: between 2.6and 4.1,in a solution containing the equivalent of 0.7mg of cefixime per mL.
Water,Method Iá921ñ: between 9.0%and 12.0%.
Tetrabutylammonium hydroxide solution,Mobile phase,Monobasic potassium phosphate solution,pH7.0Phosphate buffer,Resolution solution,and Chromatographic system Proceed as directed in the Assay.
Standard solution Use the Standard preparationprepared as directed in the Assay.
Test solution Use the Assay preparation.
Procedure Inject a volume (about 10µL)of the Test solutioninto the chromatograph,record the chromatogram,and measure the peak areas.Calculate the percentage of each impurity in the portion of Cefixime taken by the formula:
0.1P(ri/rS),in whichPis the potency,in µg per mg,of cefixime calculated in the Assay;riis the peak area for each impurity;and rSis the cefixime peak area:not more than 1.0%of any individual impurity is found;and not more than 2.0%of total impurities is found.
Tetrabutylammonium hydroxide solution Dilute 25mLof 0.4Mtetrabutylammonium hydroxide solution with water to obtain 1000mLof solution,and adjust with 1.5Mphosphoric acid to a pHof 6.5.
Mobile phase Prepare a suitable filtered and degassed mixture of Tetrabutylammonium hydroxide solutionand acetonitrile (3:1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Monobasic potassium phosphate solution Dissolve 6.8g of monobasic potassium phosphate in water to make 500mLof solution.
pH7.0Phosphate buffer Dissolve 7.1g of anhydrous dibasic sodium phosphate in water to make 500mLof solution.Adjust a volume of this solution with a sufficient volume of Monobasic potassium phosphate solutionto a pHof 7.0.
Resolution solution Dissolve USP Cefixime RSin water to obtain a solution having a concentration of about 1mg per mL.Heat this solution at 95in an oil bath for 45minutes,cool,and use promptly.
Standard preparation Dissolve an accurately weighed quantity of USP Cefixime RSin pH7.0Phosphate bufferto obtain a solution having a known concentration of about 0.2mg of cefixime (C16H15N5O7S2)per mL.Use this solution promptly.
Assay preparation Transfer about 110mg of Cefixime,accurately weighed,to a 100-mLvolumetric flask,dilute with pH7.0Phosphate bufferto volume,and mix.Transfer 10.0mLof this solution to a 50-mLvolumetric flask,dilute with pH7.0Phosphate bufferto volume,and mix.Use this solution promptly.
Chromatographic system (see Chromatography á621ñ) The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×12.5-cm column containing 4-µm packing L1.The flow rate is adjusted so that the retention time of cefixime is about 10minutes.The column is maintained at a constant temperature of about 40.Chromatograph the Resolution solution,and record the peak areas as directed for Procedure:the relative retention times are about 0.9for cefixime (E)-isomer and 1.0for cefixime;and the resolution,R,between cefixime and cefixime (E)-isomer is not less than 2.0.Chromatograph the Standard preparation,and record the peak areas as directed for Procedure:the column efficiency is not less than 4000theoretical plates when calculated by the formula:
5.545(t/Wh/2)2,the tailing factor for the analyte peak is not less than 0.9and not more than 2.0,when calculated by the formula:
W0.1/2f,in which W0.1is width of peak of 10%height;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity,in µg,of cefixime (C16H15N5O7S2)in each mg of Cefixime taken by the formula:
500,000(C/W)(rU/rS),in which Cis the concentration,in mg per mL,of cefixime in the Standard preparation;Wis the quantity,in mg,of Cefixime taken to prepare the Assay preparation;and rUand rSare the cefixime peak areas 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
USP28NF23Page 379Pharmacopeial Forum:Volume No.29(3)Page 616