(sef ox' i tin soe' dee um).
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 3-[[(aminocarbonyl)oxy]methyl]-7-methoxy-8-oxo-7-[(2-thienylacetyl)-amino]-, sodium salt (6R-cis)-.
Sodium (6R,7S)-3-(hydroxymethyl)-7-methoxy-8-oxo-7-[2-(2-thienyl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate carbamate (ester) [33564-30-6; 35607-66-0].
» Cefoxitin Sodium contains the equivalent of not less than 927 µg and not more than 970 µg of cefoxitin (C16H17N3O7S2) per mg, corresponding to not less than 97.5 percent and not more than 102.0 percent of cefoxitin sodium (C16H16N3NaO7S2), calculated on the anhydrous and acetone- and methanol-free basis.
Packaging and storage Preserve in tight containers, and store in a cold place.
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
USP Endotoxin RS
A: The chromatogram of the Assay preparation obtained as directed in the Assay exhibits a major peak for cefoxitin, the retention time of which corresponds to that exhibited in the chromatogram of the Standard preparation obtained as directed in the Assay.
Solution: 20 µg per mL.
Medium: phosphate buffer (prepared by dissolving 1.0 g monobasic potassium phosphate and 1.8 g of anhydrous dibasic sodium phosphate in water to make 1000 mL).
C: A solution (1 in 20) responds to the tests for Sodium 191.
Specific rotation 781S: between +206 and +214, calculated on the anhydrous and acetone- and methanol-free basis.
Test solution: 10 mg per mL, in methanol.
Crystallinity 695: meets the requirements.
pH 791: between 4.2 and 7.0, in a solution containing 100 mg per mL.
Water, Method I 921: not more than 1.0%, a mixture of ethylene glycol and pyridine (3:1) being used in place of methanol in the titration vessel.
Heavy metals, Method II 231: 0.002%.
Limit of acetone and methanol
Standard preparation Transfer 5.0 mL of acetone to a 1000-mL volumetric flask, dilute with water to volume, and mix (Solution A). Transfer 5.0 mL of methanol to a 1000-mL volumetric flask, dilute with water to volume, and mix (Solution B). Transfer 50.0 mL of Solution A and 5.0 mL of Solution B to a 500-mL volumetric flask, dilute with water to volume, and mix to obtain a solution having concentrations of acetone and methanol of 0.050% and 0.005% (v/v), respectively.
Test preparation Transfer 5.0 g of Cefoxitin Sodium to a 50-mL volumetric flask, dissolve in and dilute with water to volume, and mix. Transfer 3.0 mL of the resulting solution to a 15-mL centrifuge tube, cool in an ice-water bath for 2 minutes, and add 3.0 mL of 0.24 N hydrochloric acid while swirling vigorously. Centrifuge to obtain a clear solution (Test preparation).
Chromatographic system (see Chromatography 621)The gas chromatograph is equipped with a flame-ionization detector, and contains a 1.8-m × 6.3-mm glass column containing support S2, and a pre-column packed with 60- to 80-mesh silane-treated glass beads. The injection port is maintained at 100, the columns are maintained at 110, the detector is maintained at 200, and nitrogen is used as the carrier gas at a flow rate of about 50 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed under Procedure: the column efficiency determined from the acetone and methanol peaks is not less than 160 and 200 theoretical plates, respectively; the tailing factors for the acetone and methanol peaks are not more than 1.3 and 2.3, respectively; and the relative standard deviation for replicate injections is not more than 5%.
Procedure [noteUse peak areas where peak responses are indicated. ] Separately inject equal volumes (about 2 µL) of the Standard preparation and the Test preparation into the chromatograph, record the chromatograms, and measure the acetone and methanol peak responses. Calculate the percentages of acetone and methanol in the Cefoxitin Sodium taken by the same formula:
DP/C(rU / rS)in which D is the density of acetone and methanol at 20 in g per mL; P is the percentage (v/v) of acetone or methanol in the Standard preparation; C is the concentration, in g per mL, of Cefoxitin Sodium in the Test preparation; and rU and rS are the acetone or methanol peak responses of the Test preparation and the Standard preparation, respectively: not more than 0.7% of acetone and 0.1% of methanol are found.
Other requirements Where the label states that Cefoxitin Sodium is sterile, it meets the requirements for Sterility and Bacterial endotoxins under Cefoxitin for Injection. Where the label states that Cefoxitin Sodium must be subjected to further processing during the preparation of injectable dosage forms, it meets the requirements for Bacterial endotoxins under Cefoxitin for Injection.
Mobile phase Prepare a suitable mixture of water, acetonitrile, and glacial acetic acid (840:160:10), filter through a membrane filter (1 µm or finer porosity), and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Phosphate buffer Dissolve 1.0 g of monobasic potassium phosphate and 1.8 g of dibasic sodium phosphate in 900 mL of water, adjust with phosphoric acid or 10 N sodium hydroxide to a pH of 7.1 ± 0.1, dilute with water to make 1000 mL, and mix. Filter through a membrane filter of 1 µm or finer porosity.
Standard preparation Dissolve an accurately weighed quantity of USP Cefoxitin RS in Phosphate buffer to obtain a solution having a known concentration of about 0.3 mg per mL. [noteSonicate, if necessary, to dissolve the specimen. ] Use this solution within 5 hours.
Assay preparation Transfer about 150 mg of Cefoxitin Sodium, accurately weighed, to a 500-mL volumetric flask, dissolve in and dilute with Phosphate buffer to volume, and mix. Use this solution within 5 hours.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30-cm column that contains 5- to 10-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed under Procedure: the column efficiency determined from the analyte peak is not less than 2800 theoretical plates, the tailing factor for the analyte peak is not more than 1.5, and the relative standard deviation for replicate injections is not more than 1.0%.
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 responses for the major peaks. Calculate the quantity, in µg, of cefoxitin (C16H17N3O7S2) per mg of the Cefoxitin Sodium taken by the formula:
500(CP / W)(rU / rS)in which C is the concentration, in mg per mL, of USP Cefoxitin RS in the Standard preparation; P is the potency, in µg per mg, of USP Cefoxitin RS; W is the quantity, in mg, of Cefoxitin Sodium taken to prepare the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2563