(sef'' oh tye' am hye'' droe klor' ide).
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 790 µg and not more than 925 µg 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.
USP Reference standards 11
Solution: 20 µg per mL.
B: The retention time of the cefotiam peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation as obtained in the Assay.
Crystallinity 695: 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 151, the test dose being 1.0 mL per kg of a solution in pyrogen-free sodium carbonate solution (prepared by dissolving 25.6 g of sodium carbonate, previously heated at 170 for not less than 4 hours, in 1000 mL of Sterile Water for Injection) containing 40 mg per mL.
Sterility 71 Where the label states that it is sterile, it meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined.
Water, Method I 921: not more than 7.0%, the Test Preparation being prepared as directed for a hygroscopic specimen, except to use a mixture of 20 mL of formamide (previously dried over anhydrous sodium sulfate for 24 hours) and methanol (2:1), instead of methanol, to dissolve the specimen, and to determine the water content of the formamide and methanol mixture.
Mobile phase Dissolve 13.1 g of ammonium sulfate in 850 mL of water, adjust with 2 N ammonium hydroxide to a pH of 6.5 ± 0.1, add 150 mL of acetonitrile, and mix. Filter through a suitable filter of 0.5 µm or finer porosity, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
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 1000 µg of cefotiam (C18H23N9O4S3) per mL. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix. This solution contains the equivalent of about 50 µg of cefotiam (C18H23N9O4S3) per mL. Use this solution without delay.
Assay preparation Transfer about 60 mg of Cefotiam Hydrochloride, accurately weighed, to a 50-mL volumetric flask, add water to volume, and mix. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix. Use this solution without delay.
System suitability solution Prepare a solution of USP Cefotiam Hydrochloride RS in water containing about 1 mg per mL. Heat this solution at 95 for 3 minutes, and cool. Transfer 1 mL of this solution to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)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 1.5 mL per 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 1985 theoretical plates when calculated by the formula:
5.545(tr / Wh / 2)2the 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 0.6 for de-tetrazol-cefotiam and 1.0 for 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 10 µL) of the Standard preparation and the Assay preparation into 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 C is the concentration, in µg per mL, of cefotiam (C18H23N9O4S3) in the Standard preparation, based on the quantity of USP Cefotiam Hydrochloride RS taken to prepare the Standard preparation, the designated cefotiam (C18H23N9O4S3) content, in µg per mg, of USP Cefotiam Hydrochloride RS, and the extent of dilution; W is the weight, in mg, of Cefotiam Hydrochloride taken to prepare the Assay preparation; and rU and rS are the cefotiam peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 2562