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Category Antibacterial (second-generation cephalosporin).

          Cefuroxime Sodium for Injection is a sterile material consisting of Cefuroxime Sodium with or without excipients. It contains the equivalent of not less than 90.0 per cent and not more than 120.0 per cent of the labelled amount of C₁₆H₁₆N₄O₈S.

Strengths available 0.75, 1.5 and 7.5 g (base).

Dose Adults: Deep Intramuscular or intravenous, 750 mg to 3 g every 8 hours.
          Children and infants over 3 months: Deep Intramuscular or intravenous, 50 to 100 mg per kg of body weight daily in equally divided doses every 6 to 8 hours.

Contra-indication; Additional information See under Cephalexin, p. 58.

Warning
          1. Pain at the injection site has been reported with intramuscular administration, and thrombophlebitis may occur with intravenous administration.
          2. It may cause transient increase in serum aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase concentrations and jaundice. See also under Cephalexin, p. 58.

Packaging and storage Cefuroxime Sodium for Injection shall be kept in Containers for Sterile Solids as described under “Parenteral Preparations” (Appendix 1.16), protected from light, and stored at a temperature not exceeding 30º.

Labelling The label on the container states the quantity equivalent to the amount of cefuroxime.

Identification
          A. The infrared absorption spectrum is concordant with the spectrum obtained from Cefuroxime Sodium RS (Appendix 2.1) or with the reference spectrum of Cefuroxime Sodium.
          B. The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.           
          C. Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using silica gel HF254 as the coating substance and a mixture of 10 volumes of tetrahydrofuran and 90 volumes of a 15.0 per cent w/v solution of ammonium acetate, previously adjusted to pH 6.2 with glacial acetic acid as the mobile phase. Apply separately to the plate, 1 μl of each of the following solutions. For solution (A) dissolve a quantity of the contents of a sealed container in sufficient of a mixture of equal volumes of methanol and 0.067 M mixed phosphate buffer pH 7.0 to produce a solution containing the equivalent of 400 μg ml of cefuroxime. Solution (B) contains 4 mg per ml of Cefuroxime Sodium RS in a mixture of equal volumes of methanol and 0.067 M mixed phosphate buffer pH 7.0. Solution (C) contains 400 μg per ml each of Cefuroxime Sodium RS and Cefoxitin Sodium RS in a mixture of equal volumes of methanol and 0.067 M mixed phosphate buffer pH 7.0. After removal of the plate, allow it to dry in a current of warm air, and examine under ultraviolet (254 nm): the principal spot in the chromatogram obtained from solution (A) corresponds to that obtained from solution (B). The test is not valid unless the chromatogram obtained from solution (C) shows two clearly separated principal spots.
          D. It yields the reactions characteristic of sodium salts (Appendix 5.1).

Clarity of solution A solution containing the equivalent of 10.0 per cent w/v of cefuroxime in carbon dioxide-free water is not more opalescent than reference suspension II (Appendix 4.1).

Constituted solution At the time of use, complies with the requirements described under “Constituted Solutions” (Appendix 4.20).

pH 5.5 to 8.5, in a 10.0 per cent w/v solution (Appendix 4.11).

Water Not more than 3.5 per cent w/w (Karl Fischer Method, Appendix 4.12). Use 400 mg.

Particulate matter Complies with the requirements described under “Particulate Matter in Injections” (Small-volume Injections, Appendix 4.27).

Related substances Carry out the test as described under Assay using Assay preparation, Resolution solution, and Standard preparation 2.
          In the chromatogram obtained from the Assay preparation, determine the percentage content of related substances by using the area of the principal peak in the chromatogram obtained from the Standard preparation 2 (1.0 per cent) as a comparison area.
     Limits

Disregard limit Not more than 0.1 times the comparison area (0.1 per cent).

Impurity A (descarbamoylcefuroxime) Not more than the comparison area (1.0 per cent).

Any other impurity Not more than the comparison area (1.0 per cent).

Total Not more than 3 times the comparison area (3.0 per cent). 

Bacterial endotoxins When tested as described in the “Test for Bacterial Endotoxins” (Appendix 8.5), it contains not more than 0.10 Endotoxin Unit per mg of cefuroxime.

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).
          Mobile phase Prepare a mixture of 1 volume of acetonitrile and 99 volumes of an acetate buffer solution pH 3.4 prepared by dissolving 6.01 g of glacial acetic acid and 0.68 g of sodium acetate in water and diluting to 1000.0 ml with the water. Make adjustments if necessary.
          Standard preparation 1 Dissolve an accurately weighed quantity of Cefuroxime Sodium RS in water to obtain a solution having a known concentration of about 1 mg per ml.
          Standard preparation 2 Dilute 1 volume of Standard preparation 1 to 100 volumes.
          Assay preparation Dissolve an accurately weighed quantity of mixed contents of the 10 containers of Cefuroxime Sodium for Injection in water to produce a solution containing the equivalent of about 1 mg per ml.
          Resolution solution Heat 20 ml of Standard preparation 1 in a water-bath at 60º for 10 minutes, cool and inject immediately.
          Chromatographic system​ The chromatographic procedure may be carried out using (a) a stainless steel column (12.5 cm × 4.6 mm) packed with trimethyl group chemically bonded to porous silica or ceramic microparticles (5 μm), (b) Mobile phase at a flow rate of about 1.5 ml per minute, and (c) an ultraviolet photometer set at 273 nm.
          To determine the suitability of the chromatographic system, chromatograph Resolution solution, and record the peak responses as directed under Procedure: the resolution factor between cefuroxime and descabamoylcefuroxime peaks is not less than 2.0 and the symmetry factor of cefuroxime peak is not more than 1.5.
          Procedure Separately inject equal volumes (about 20 μl) of Standard preparation 1 and Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks.
          Calculation Calculate the content of C₁₆H₁₆N₄O₈S, in each ml of the Injection taken, using the declared content of C₁₆H₁₅N₄O₈S.Na in Cefuroxime Sodium RS. Each mg of C₁₆H₁₅N₄O₈S.Na is equivalent of 0.9508 mg of C₁₆H₁₆N₄O₈S.

Other requirements Complies with the requirements described under “Parenteral Preparations” (Appendix 1.16).