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Category Antibacterial (third-generation cephalosporin).

          Cefotaxime Sodium for Injection is a sterile material consisting of Cefotaxime Sodium with or without excipients. It contains an amount of cefotaxime sodium equivalent to not less than 90.0 per cent and not more than 115.0 per cent of the labelled amount of C₁₆H₁₇N₅O₇S₂.

Strengths available 0.5, 1 and 10 g (base).

Dose Adults: Deep intramuscular or intravenous, 2 to 6 g daily in 2 to 4 divided doses or up to 12 g daily.
          Children: Deep intramuscular or intravenous, 100 to 150 mg per kg of body weight daily in 2 to 4 divided doses.

Contra-indication; Warning; Precaution; Additional information See under Cefotaxime Sodium, p. 43.

Packaging and storage Cefotaxime 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 cefotaxime.

Identification
          A. The infrared absorption spectrum is concordant with the spectrum obtained from Cefotaxime Sodium RS (Appendix 2.1) or with the reference spectrum of Cefotaxime 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 15 volumes of acetone and 85 volumes of a 15.4 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 4 mg per ml of cefotaxime. Solution (B) contains 4 mg per ml of Cefotaxime Sodium RS in a mixture of equal volumes of methanol and 0.067 M mixed phosphate buffer pH 7. Solution (C) contains 4 mg per ml each of Cefotaxime Sodium RS and Cefoxitin Sodium RS in a mixture of equal volumes of methanol and 0.067 M mixed phosphate buffer pH 7. After removal of the plate, allow it to dry in air and examine under ultraviolet light (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 with solution (C) shows two clearly separated 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 cefotaxime in carbon dioxide-free water is clear (Appendix 4.1). The absorbance of the solution at 430 nm is not greater than 0.60 (Appendix 2.2).

pH 4.5 to 6.5, in a 10.0 per cent w/v solution (Appendix 4.11).

Loss on drying Not more than 3.0 per cent w/w after drying at 100º to 105º for 3 hours, (Appendix 4.15).

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

Bacterial endotoxins When tested as described in the “Test for Bacterial Endotoxins” (Appendix 8.5), it contains not more than 0.20 Endotoxin Unit per mg of cefotaxime.

Related substances Carry out the test as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).
          Mobile phase Use a mixture prepared by dissolving 3.5 g of potassium dihydrogenphosphate and 11.6 g of disodium hydrogenphosphate in 1000 ml of water at pH 7.0 and adding 375 ml of methanol.
          Standard preparation Use a 0.0011 per cent w/v solution of Cefotaxime Sodium RS in Mobile phase.
          Test solution Dissolve a quantity of the contents of the sealed container in sufficient of Mobile phase to produce a solution containing the equivalent of 0.1 per cent w/v of cefotaxime.
          The chromatographic conditions described under Assay may be used.
          Procedure Separately inject 10 μl each solution. Allow the chromatography to proceed for at least 8 times the retention time (about 6 minutes) of cefotaxime. In the chromatogram obtained from Test solution the area of any secondary peak is not more than the area of the principal peak in the chromatogram obtained from Standard solution (1 per cent) and the sum of the areas of all the secondary peaks is not more than 4 times the area of the principal peak in the chromatogram obtained from Standard solution (4 per cent).
Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).
          Mobile phase Dissolve 3.5 g of potassium
dihydrogenphosphate and 11.6 g of disodium
hydrogenphosphate in 1000 ml of water at pH 7.0 and add
375 ml of methanol. Make adjustments if necessary.
          Standard preparation Dissolve an accurately weighed quantity of Cefotaxime Sodium RS in Mobile phase and dilute quantitatively to obtain a solution having a known concentration of about 100 μg per ml.
          Assay preparation Dissolve an accurately weighed quantity of the mixed contents of the 10 containers of Cefotaxime Sodium for Injection in Mobile phase and dilute quantitatively to produce a solution containing about 100 μg of cefotaxime per ml.
          Resolution solution Add 1.0 ml of 2 M hydrochloric acid to 4.0 ml of Assay preparation. Heat the solution at 40º for 2 hours. Add 5.0 ml of Phosphate buffer solution pH 6.6 and 1.0 ml of 2 M sodium hydroxide.
          Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (5 μm), (b) Mobile phase at a flow rate of about 1 ml per minute, and (c) an ultraviolet photometer set at 235 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 two principal peaks is not less than 3.5 and the symmetry factor of cefotaxime peak is less than 2.0. Chromatograph Standard preparation, and record the peak responses as directed under Procedure: the relative standard deviation for replicate injections is not more than 2.0 per cent.
          Procedure Separately inject equal volumes (about 10 μl) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks.
          Calculation Calculate the content of C₁₆H₁₇N₅O₇S₂ in the portion of the Injection taken, using the declared content of C₁₆H₁₆N₅O₇S₂.Na in Cefotaxime Sodium RS. Each mg of C₁₆H₁₆N₅O₇S₂.Na is equivalent to 0.9540 mg of C₁₆H₁₇N₅O₇S₂.

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