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Category Antibacterial (first-generation cephalosporin).

          Cefazolin Sodium contains not less than 89.1 per cent and not more than 110.1 per cent of C₁₄H₁₃N₈O₄S₃.Na, calculated on the anhydrous basis.

Description White or almost white powder.

Solubility Freely soluble in water; very slightly soluble in ethanol; practically insoluble in chloroform and in ether.

Contra-indication It is contra-indicated in patients who have shown hypersensitivity to any member of the cephalosporins.

Warning
          1. Cephalosporins should be avoided in patients who have had an immediate-type (anaphylactic) hypersensitivity reaction to penicillins and should be administered with caution in patients who have had a delayed- type (e.g., rash, fever, eosinophilia) reaction to penicillins or other drugs.
          2. It may cause local reaction at the injection site, phlebitis and thrombophlebitis upon intraveneous administration, CNS side effects, hematological abnormalities especially hypoprothrombinemia, gastrointestinal disturbances, pseudomembranous colitis, and hypersensitivity reactions.
          3. It should be administered with caution in patients with markedly impaired renal function or with a history of gastro-intestinal diseases, particularly colitis.
          4. Risk-benefit should be considered if it is to be used in pregnant or nursing women.

Additional information
          1. Cefazolin is used as an alternative to amoxicillin or ampicillin for prophylaxis against beta-hemolytic (viridans group) streptococcal endocarditis in penicillinallergic individuals considered to be at risk for bacterial endocarditis following certain dental or upper respiratory tract procedures.
          2. Cefazolin sodium can be administered intramuscularly by injection into a large muscle mass or intravenously by direct injection or by intermittent or continuous infusion. Total daily dosages are the same for intraveneous and intramuscular administration.
          3. Cefazolin causes less pain on intramuscular injection than other first-generation cephalosporins. In addition, cefazolin is preferred to other first-generation cephalosporins because it has superior pharmacokinetics properties that result in higher and more sustained serum concentrations.

Packaging and storage Cefazolin Sodium shall be kept in tightly closed containers, protected from light and stored at a temperature not exceeding 25º. If it is intended for parenteral administration, it shall also be kept under sterile condition.

Labelling The label on the container states (1) storage condition; (2) parenteral grade.

Identification
          A. The infrared absorption spectrum is concordant with the spectrum obtained from Cefazolin Sodium RS (Appendix 2.1) or with the reference spectrum of Cefazolin 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. It yields the reactions characteristic of sodium salts (Appendix 5.1).

Appearance of solution Dissolve 2.50 g in carbon dioxide-free water and dilute to 25.0 ml with the same solvent. The resulting solution is clear (Appendix 4.1) and its absorbance at 430 nm is not more than 0.15 (Appendix 2.2).

pH 4.0 to 6.0, in a 10.0 per cent w/v solution (Appendix 4.11).

Specific rotation –10.0º to –24.0º, calculated on the anhydrous basis, determined in a 5.5 per cent w/v solution in 0.1 M sodium hydrogencarbonate (Appendix 4.8).

Absorbance Dissolve 100 mg in water and dilute to 100.0 ml with the same solvent. Dilute 2.0 ml of the solution to 100.0 ml with a 4.2 per cent w/v solution of sodium hydrogencarbonate. The light absorption spectrum of the diluted solution, when observed between 220 nm and 350 nm, exhibits a maximum at about 272 nm; the specific absorbance at this maximum is between 260 and 300, calculated on the anhydrous basis (Appendix 2.2).

Water Not more than 6.0 per cent w/w (Karl Fischer Method, Appendix 4.12). Use 300 mg.

N,N-Dimethylaniline Not more than 20 ppm (Appendix 5.16).

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).

          Phosphate buffer pH 3.6 Dissolve 900 mg of anhydrous disodium hydrogenphosphate and 1.298 g of citric acid monohydrate in water to make 1000 ml.
          Phosphate buffer pH 7.0 Dissolve 5.68 g of anhydrous disodium hydrogenphosphate and 3.63 g of potassium dihydrogenphosphate in water to make 1000 ml.
          Mobile phase Prepare a mixture of 1 volume of acetonitrile and 9 volumes of Phosphate buffer pH 3.6. Make adjustments if necessary.
          Internal standard solution Transfer 750 mg of salicylic acid to a 100-ml volumetric flask, dissolve in 10 ml of methanol, dilute with Phosphate buffer pH 7.0 to volume, and mix.
          Standard preparation Transfer about 25 mg of Cefazolin RS, accurately weighed, to a 25-ml volumetric flask, dissolve in and dilute with Phosphate buffer pH 7.0 to volume and mix. Transfer 5.0 ml of this solution to a 100-ml volumetric flask, add 5.0 ml of Internal standard solution, dilute with Phosphate buffer pH 7.0 to volume and mix.
          Assay preparation Transfer about 50 mg of Cefazolin Sodium, accurately weighed, to a 50-ml volumetric flask, dissolve in and dilute with Phosphate buffer pH 7.0 to volume, and mix. Transfer 5.0 ml of this solution to a 100-ml volumetric flask, add 5.0 ml of Internal standard solution, dilute with Phosphate buffer pH 7.0 to volume, and mix.
          Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (30 cm × 4.0 mm) packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (10 μm), (b) Mobile phase at a flow rate of about 2 ml per minute, and (c) an ultraviolet photometer set at 254 nm.
          To determine the suitability of the chromatographic system, chromatograph Standard preparation, and record the peak responses as directed under Procedure: the resolution factor between cefazolin and salicylic acid peaks is not less than 4.0, the symmetry factor is not more than 1.5 and the relative standard deviation for replicate injections is not more than 2.0 per cent. The relative retention times are about 0.7 for salicylic acid and 1.0 for cefazolin.
          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 C₁₄H₁₃N₈O₄S₃.Na in the Cefazolin Sodium taken, using the declared content of C₁₄H₁₄N₈O₄S₃ in Cefazolin RS. Each mg of C₁₄H₁₄ N₈O₄S₃ is equivatent to 1.0484 mg of C₁₄H₁₃N₈O₄S₃.Na.