Cefmenoxime Hydrochloride
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5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid,7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-,hydrochloride (2:1),[6R-[6a,7b(Z)]]-.
(6R,7R)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-3-[[(1-methyl-1H-tetrazol-5-yl)-thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 72-(Z)-(O-methyloxime),hydrochloride (2:1) [75738-58-8].
»Cefmenoxime Hydrochloride contains the equivalent of not less than 869µg and not more than 1015µg of cefmenoxime (C16H17N9O5S3)per mg,calculated on the anhydrous 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.
Identification—
Solution:
25µg per mL.
Medium:
pH6.8buffer (prepared as directed in the Assay).
B:
The retention time of the cefmenoxime peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,both relative to the internal standard,as obtained in the Assay.
Crystallinity á695ñ:
meets the requirements.
Pyrogen á151ñ—
Where the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms,it meets the requirements,the test dose being 1.0mLper kg of a solution in pyrogen-free sodium carbonate solution (prepared by dissolving 14.0g of sodium carbonate,previously heated at 170
for not less than 4hours,in 1000mLof sterile water for injection)containing 60mg per mL.
for not less than 4hours,in 1000mLof sterile water for injection)containing 60mg per mL.
Sterility á71ñ—
Where the label states that it is sterile,it meets the requirements when tested as directed for Membrane Filtrationunder Test for Sterility of the Product to be Examined,except to use Fluid Ato each 100mLof which has been added 2.0g of sodium carbonate previously sterilized by heating at 180for 2hours.
for 2hours.
Water,Method Iá921ñ:
not more than 1.5%,the Test Preparationbeing prepared as directed for a hygroscopic specimen,except to use 20mLof a mixture of formamide (previously dried over anhydrous sodium sulfate for 24hours)and methanol (2:1),instead of methanol,to dissolve the specimen,to use two 5-mLportions of the same formamide and methanol mixture to rinse the container,and to determine the water content of the formamide and methanol mixture.
Assay—
pH6.8buffer—
Dissolve 6.4g of monobasic potassium phosphate and 18.9g of dibasic sodium phosphate in 750mLof water,adjust with 1Nsodium hydroxide to a pHof 6.8±0.1,dilute with water to 1000mL,and mix.
Mobile phase—
Prepare a suitable mixture of water,acetonitrile,and glacial acetic acid (50:10:1).Filter through a suitable filter of 0.5µm or finer porosity,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Internal standard solution—
Prepare a solution of phthalimide in methanol containing 1.5mg per mL.
Standard preparation—
Transfer about 50mg of USP Cefmenoxime Hydrochloride RS,accurately weighed,to a 50-mLvolumetric flask,add 10mLof pH6.8buffer,and dissolve by swirling.Dilute with Mobile phaseto volume,and mix.Transfer 4.0mLof this solution to a second 50-mLvolumetric flask,add 20.0mLof Internal standard solution,dilute with Mobile phaseto volume,and mix.This solution contains the equivalent of about 80µg of cefmenoxime (C16H17N9O5S3)per mL.
Assay preparation—
Transfer about 50mg of Cefmenoxime Hydrochloride,accurately weighed,to a 50-mLvolumetric flask,add 10mLof pH6.8buffer,and dissolve by swirling.Dilute with Mobile phaseto volume,and mix.Transfer 4.0mLof this solution to a second 50-mLvolumetric flask,add 20.0mLof Internal standard solution,dilute with Mobile phaseto volume,and mix.
Chromatographic system
(see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4-mm ×15-cm column that contains packing L1.The flow rate is about 1mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the resolution,R,between the phthalimide and the cefmenoxime peaks is not less than 2.3,the column efficiency,determined from the cefmenoxime peak,is not less than 1200theoretical plates when calculated by the formula:
5.545(tr/Wh/2)2,
the tailing factor for the cefmenoxime peak is not more than 1.6,and the relative standard deviation of replicate injections is not more than 2.0%.
Procedure—
[NOTE—Use peak areas where peak responses are indicated.]Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in µg,of cefmenoxime (C16H17N9O5S3)in each mg of the Cefmenoxime Hydrochloride taken by the formula:
(WSPS/WU)(RU/RS),
in which WSis the weight,in mg,of USP Cefmenoxime Hydrochloride RStaken to prepare the Standard preparation,PSis the designated cefmenoxime (C16H17N9O5S3)content,in µg per mg,of USP Cefmenoxime Hydrochloride RS,WUis the weight,in mg,of Cefmenoxime Hydrochloride taken to prepare the Assay preparation,and RUand RSare the peak response ratios of the cefmenoxime peak to the internal standard peak 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
USP28–NF23Page 381
Phone Number:1-301-816-8335