Cefotiam Hydrochloride
Click to View Image
C18H23N9O4S3·2HCl 598.56

5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid,7[[-(2-amino-4-thiazolyl)acetyl]-amino]-3-[[[1-[2-(dimethylamino)ethyl]-1H-tetrazol-5-yl]-thio]methyl]-8-oxo,hydrochloride,(6R-trans)-.

(6R,7R)-7-[2-(2-Amino-4-thiazolyl)acetamido]-3-[[[1-[2-(dimethylamino)ethyl]-1H-tetrazol-5-yl]thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid dihydrochloride.

7(R)-[2-(2-Amino-4-thiazolyl)acetamido]-3-[[[1-[2-dimethylamino)ethyl]-1H-tetrazol-5-yl]thio]methyl]-3-cephem-4-carboxylic acid dihydrochloride [66309-69-1].
»Cefotiam Hydrochloride contains the equivalent of not less than 790µg and not more than 925µg of cefotiam (C18H23N9O4S3)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: 20µg per mL.
Medium: water.
B: The retention time of the cefotiam peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparationas obtained in the Assay.
Crystallinity á695ñ: meets the requirements.
Pyrogen— 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 of the Pyrogen Test á151ñ,the test dose being 1.0mLper kg of a solution in pyrogen-free sodium carbonate solution (prepared by dissolving 25.6g of sodium carbonate,previously heated at 170for not less than 4hours,in 1000mLof Sterile Water for Injection)containing 40mg 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.
Water,Method Iá921ñ: not more than 7.0%,the Test Preparationbeing prepared as directed for a hygroscopic specimen,except to use a mixture of 20mLof formamide (previously dried over anhydrous sodium sulfate for 24hours)and methanol (2:1),instead of methanol,to dissolve the specimen,and to determine the water content of the formamide and methanol mixture.
Assay—
Mobile phase— Dissolve 13.1g of ammonium sulfate in 850mLof water,adjust with 2Nammonium hydroxide to a pHof 6.5±0.1,add 150mLof acetonitrile,and mix.Filter through a suitable filter of 0.5µm or finer porosity,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Cefotiam Hydrochloride RS,quantitatively in water to obtain a solution having a known concentration of about 1000µg of cefotiam (C18H23N9O4S3)per mL.Transfer 5.0mLof this solution to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.This solution contains the equivalent of about 50µg of cefotiam (C18H23N9O4S3)per mL.Use this solution without delay.
Assay preparation— Transfer about 60mg of Cefotiam Hydrochloride,accurately weighed,to a 50-mLvolumetric flask,add water to volume,and mix.Transfer 5.0mLof this solution to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.Use this solution without delay.
System suitability solution— Prepare a solution of USP Cefotiam Hydrochloride RSin water containing about 1mg per mL.Heat this solution at 95for 3minutes,and cool.Transfer 1mLof this solution to a 100-mLvolumetric flask,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 ×25-cm column that contains packing L1.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency,determined from the cefotiam peak,is not less than 1985theoretical plates when calculated by the formula:
5.545(tr/Wh /2)2,
the tailing factor for the cefotiam peak is not more than 1.8,and the relative standard deviation for replicate injections is not more than 1.0%.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.6for de-tetrazol-cefotiam and 1.0for cefotiam;and the resolution,R,between the de-tetrazol-cefotiam peak and the cefotiam peak is not less than 4.0.
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 cefotiam (C18H23N9O4S3)in each mg of the Cefotiam Hydrochloride taken by the formula:
1000(C/W)(rU/rS),
in which Cis the concentration,in µg per mL,of cefotiam (C18H23N9O4S3)in the Standard preparation,based on the quantity of USP Cefotiam Hydrochloride RStaken to prepare the Standard preparation,the designated cefotiam (C18H23N9O4S3)content,in µg per mg,of USP Cefotiam Hydrochloride RS,and the extent of dilution;Wis the weight,in mg,of Cefotiam Hydrochloride taken to prepare the Assay preparation;and rUand rSare the cefotiam peak 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
USP28–NF23Page 392
Phone Number:1-301-816-8335