(sef'' oh tax' eem soe' dee um).
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-[6,7(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 916 µg and not more than 964 µg of cefotaxime (C16H17N5O7S2) per mg, calculated on the dried basis.
Packaging and storage Preserve in tight containers.
USP Reference standards 11
USP Endotoxin RS
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 2.5 g of it to a 25-mL volumetric 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 430 nm in a 1-cm cell, using carbon dioxide-free water as the blank: its absorbance is not more than 0.20. Transfer 10 mL of the solution to a glass test tube, add 1 mL of glacial acetic acid, mix, and examine immediately: the solution is clear.
B: The chromatogram of the Assay obtained as directed in the Assay exhibits a major peak for cefotaxime, the retention time of which corresponds to that exhibited in the chromatogram of the Standard preparation obtained as directed in the Assay.
C: It responds to the tests for Sodium 191.
Specific rotation 781S: between +58 and +64.
Test solution: 10 mg per mL, in water.
pH 791: between 4.5 and 6.5, in a solution (1 in 10).
Loss on drying 731 Dry it at 100 to 105 for 3 hours: it loses not more than 3.0% of its weight.
Chromatographic purity Using the chromatogram of the Assay preparation obtained in the Assay, calculate the percentage of each impurity by the formula:
100ri / (ris + rc)in which ri is the peak area response of a given impurity; ris is the sum of all of the impurity peak area responses; and rc is 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 71 when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined, and for Bacterial endotoxins under 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 endotoxins under Cefotaxime for Injection.
0.05 M Phosphate Buffer Dissolve 7.1 g of anhydrous dibasic sodium phosphate in 1000 mL of water, and adjust with phosphoric acid to a pH of 6.25.
Solution A Prepare a mixture of 0.05 M Phosphate Buffer and methanol (86:14). Pass through a filter having a porosity of 0.5 µm or less, and degas before use.
Solution B Prepare a mixture of 0.05 M Phosphate Buffer and methanol (60:40). Pass through a filter having a porosity of 0.5 µm or less, and degas before use.
Mobile phase Use variable mixtures of Solution A and Solution B as directed for Chromatographic system.
Standard preparation Transfer about 40 mg of USP Cefotaxime Sodium RS, accurately weighed, to a 50-mL volumetric flask, add about 40 mL of Solution A, swirl to dissolve, dilute with Solution A to volume, and mix. [noteUse this solution promptly. It may be used within 24 hours if stored in the refrigerator. ]
Sensitivity solution Transfer 2.0 mL of Standard preparation to a 100-mL volumetric flask, dilute with Solution A to volume, and mix. Transfer 2.0 mL of this solution to a 20-mL volumetric flask, dilute with Solution A to volume, and mix.
Resolution solution Mix 1 mL of Standard preparation, 7.0 mL of water, and 2.0 mL of methanol. Add 25 mg of sodium carbonate, mix, and allow to stand at room temperature for 10 minutes, with occasional swirling. Add 3 drops of glacial acetic acid and 1 mL of Standard preparation, and mix.
Assay preparation Transfer about 40 mg of Cefotaxime Sodium, accurately weighed, to a 50-mL volumetric flask, add Solution A to dissolve it, dilute with Solution A to volume, and mix. [noteUse this solution promptly. It may be used within 24 hours if stored in a refrigerator. ]
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 235-nm detector and a 3.9-mm × 15-cm column that contains 5-µm packing L1 and is maintained at a constant temperature of about 30. The flow rate is about 1 mL per minute. The system is equilibrated with 100% Solution A. Seven minutes after injection of the solution under test, the proportion of Solution B is increased linearly from 0% to 20% at a rate of 10% per minute and is maintained at that composition for 7 minutes. The proportion of Solution B is then increased linearly at a rate of 2.7% per minute until the proportion of Solution B is 100%, and is held at that composition for 5 minutes, after which the proportion of Solution A is 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 3.5 minutes for desacetylcefotaxime and 14 minutes 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 for Procedure: the retention time for the main cefotaxime peak is between 12 and 15 minutes, 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 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 per mg, of cefotaxime (C16H17N5O7S2) in the portion of Cefotaxime Sodium taken by the formula:
50(CP / W)(rU / rS)in which C is the concentration, in mg per mL, of USP Cefotaxime Sodium RS in the Standard preparation; P is the designated content, in µg per mg, of cefotaxime (C16H17N5O7S2) in USP Cefotaxime Sodium RS; W is the weight, in mg, of Cefotaxime Sodium taken to prepare the Assay preparation; and rU and rS are the cefotaxime peak area responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2557