Ceftazidime for Injection
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This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
Ceftazidime for Injection is a sterile mixture of Sterile Ceftazidime and Sodium Carbonate or Arginine. It contains not less than 90.0 percent and not more than 105.0 percent of ceftazidime (C22H22N6O7S2) on the dried and sodium carbonate- or arginine-free basis, and not less than 90.0 percent and not more than 120.0 percent of the labeled amount of ceftazidime (C22H22N6O7S2).
Packaging and storage—Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for constitution, protected from light.
USP Reference standards 〈11
USP L-arginine RS
USP Ceftazidime, Delta-3-Isomer RS
USP Ceftazidime Pentahydrate RS
Identification
A: The chromatograms of the Assay preparations exhibit a major peak for ceftazidime, the retention time of which corresponds to that in the chromatogram of the Standard preparation.
B: It dissolves in 1 N hydrochloric acid with effervescence, evolving a colorless gas, which when passed into calcium hydroxide TS produces a white precipitate immediately.
Bacterial Endotoxins Test 〈85〉 —It contains not more than 0.1 USP Endotoxin Unit per mg of ceftazidime.
Sterility Tests 〈71〉 —It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined.
pH 〈791〉: between 5.0 and 7.5, in a solution constituted in the sealed container, taking care to relieve the pressure inside the container during constitution, containing 100 mg of ceftazidime per mL.
Loss on drying 〈731〉—Dry about 300 mg, accurately weighed, in vacuum at a pressure not exceeding 5 mm of mercury at 25° for 4 hours: where it contains arginine, it loses not more than 12.5% of its weight. Where it contains sodium carbonate, it loses not more than 13.5% of its weight. Where it contains arginine, use the percentage loss obtained, m, to calculate, on the dried and arginine-free basis, the result from Assay preparation 1 obtained as directed in the Assay. Where it contains sodium carbonate, heat the residue in vacuum at a pressure not exceeding 5 mm of mercury at 100° an additional 3 hours, and calculate the total percentage of weight loss. Use this percentage, m, to calculate, on the dried and sodium carbonate-free basis, the result from Assay preparation 1 obtained as directed in the Assay.
Particulate Matter in Injections 〈788〉 : meets the requirements for small-volume injections.
Sodium carbonate (where present)
Potassium chloride solution—Dissolve 19.07 g of potassium chloride in water to make 1000 mL of solution.
Standard preparation—Dissolve a suitable quantity of sodium chloride, previously dried at 105° for 2 hours and accurately weighed, in water to obtain a solution having a known concentration of about 14 µg per mL. Transfer 10 mL of this solution to a 100-mL volumetric flask, add 10.0 mL of Potassium chloride solution, dilute with water to volume, and mix.
Test preparation—Use the stock solution used to prepare Assay preparation 1 in the Assay, diluting it quantitatively, and stepwise if necessary, with water to obtain a solution containing about 12.5 µg of sodium carbonate per mL. Transfer 10.0 mL of this solution to a 100-mL volumetric flask, add 10.0 mL of Potassium chloride solution, dilute with water to volume, and mix.
Blank solution—Transfer 10.0 mL of Potassium chloride solution to a 100-mL volumetric flask, dilute with water to volume, and mix. Procedure—Concomitantly determine the absorbances of the Standard preparation and the Test preparation at the sodium emission line of 589.0 nm, with a suitable atomic absorption spectrophotometer (see Atomic Absorption Spectroscopy 〈852〉) equipped with a sodium hollow cathode lamp and an air–acetylene ame, using the Blank solution as the blank. Calculate the percentage of sodium carbonate (Na2CO3) in the portion of Ceftazidime for Injection taken by the formula:
(105.99/116.88)(0.1C/M)(AU/AS)
in which 105.99 is the molecular weight of sodium carbonate; 116.88 is twice the molecular weight of sodium chloride; C is the concentration, in µg per mL, of sodium chloride in the Standard preparation; M is the quantity, in mg, of Ceftazidime for Injection in each mL of the Test preparation, based on the quantity taken to prepare the stock solution and the extent of dilution; and AU and AS are the absorbances of the
Test preparation and the Standard preparation, respectively. Use this percentage to calculate, on the dried and sodium carbonate-free basis, the result from Assay preparation 1 obtained as directed in the Assay.
Limit of pyridine
Mobile phase—Mix 300 mL of acetonitrile and 100 mL of 0.25 M monobasic ammonium phosphate, dilute with water to obtain 1000 mL of solution, and adjust with ammonium hydroxide to a pH of 7.0 ± 0.1. Pass this solution through a lter having a 1-µm or ner porosity, and degas. Make adjustments if necessary (see System Suitability under Chromatography 〈621〉). pH 7 Buffer—Dissolve 5.68 g of anhydrous dibasic sodium phosphate and 3.63 g of monobasic potassium phosphate in water to make 1000 mL of solution.
Standard solution—Transfer about 250 mg of pyridine, accurately weighed, to a 100-mL volumetric flask, dilute with water to volume, and mix. Immediately prior to chromatography, transfer 2.0 mL of this solution to a 200-mL volumetric flask, dilute with pH 7 Buffer to volume, and mix. This solution contains about 25 µg of pyridine per mL.
Test solution—Transfer about 660 mg of Ceftazidime for Injection, just removed from its container and accurately weighed, to a 100-mL volumetric flask, promptly add pH 7 buffer to volume, and mix. Store this solution in a cool place, and use it within 1 hour. Chromatographic system (see Chromatography 〈621〉)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.6 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the tailing factor for the analyte peak is not more than 2.5; and the relative standard deviation for replicate injections is not more than 3%.
Procedure—Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas of the responses for the pyridine peaks. Calculate the percentage of pyridine in the portion of Ceftazidime for Injection taken by the formula:
10(C/W)(rU/rS)
in which C is the concentration, in µg per mL, of pyridine in the Standard solution; W is the weight, in mg, of Ceftazidime for Injection taken; and rU and rS are the pyridine peak responses obtained from the Test solution and the Standard solution, respectively: not more than 0.4% of pyridine is found where it contains sodium carbonate; and not more than 0.3% where it contains arginine.
Content of Arginine (where present)
Mobile phase—Dissolve 1.15 g of monobasic ammonium phosphate in about 800 mL of water. Adjust with phosphoric acid to a pH of 2.0 ± 0.1, dilute with water to 1000 mL, and mix. Prepare a filtered and degassed mixture of acetonitrile and this solution (750:250). Make adjustments if necessary (see System Suitability under Chromatography 〈621〉).
Standard preparation—Dissolve accurately weighed quantities of USP Ceftazidime Pentahydrate RS and USP l-Arginine RS in water to obtain a solution containing known concentrations of about 0.2 mg of each per mL.
Test preparation—Quantitatively dissolve an accurately weighed portion of Ceftazidime for Injection in water to obtain a solution having a concentration of about 0.2 mg of ceftazidime per mL.
Chromatographic system (see Chromatography 〈621〉)—The liquid chromatograph is equipped with a 206-nm detector, a 4.6-mm × 50-cm saturator pre-column containing packing L27, and a 4-mm × 25-cm analytical column containing packing L20. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the responses as directed for Procedure: the resolution, R, between the ceftazidime and the arginine peaks is not less than 6.0; and the tailing factor for the arginine peak is not more than 4.0. Procedure—Separately inject equal volumes (about 20 µL) of the Standard preparation and the Test preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of arginine (C6H14N4O2) in the Ceftazidime for Injection taken by the formula:
100(CS/CU)(rU/rS)
in which C is the concentration, in mg per mL, of USP l-Arginine RS in the Standard preparation; C is the concentration, in mg per mL, of Ceftazidime for Injection in the Test preparation, based on the weight, in mg, of Ceftazidime for Injection taken and the extent of dilution; and rU and rS are the arginine peak responses obtained from the Test preparation and the Standard preparation, respectively. Use this percentage to calculate, on the anhydrous and arginine-free basis, the assay result from Assay preparation 1 obtained as directed in the Assay. Other requirements—It meets the requirements for Uniformity of Dosage Units 〈905〉 and for Labeling 〈7〉, Labels and Labeling for Injectable Products.
Assay
pH 7 buffer, Mobile phase, Standard preparation, Resolution solution, and Chromatographic system—Proceed as directed in the Assay under Ceftazidime.
Assay preparation 1—Transfer an accurately weighed quantity of Ceftazidime for Injection, equivalent to about 250 mg of ceftazidime (C22H22N6O7S2), to a 250-mL volumetric flask, dilute with water to volume, and mix to obtain a stock solution. [Note—Protect this solution from light.] Immediately prior to chromatography, transfer 5.0 mL of this solution to a 50-mL volumetric flask, dilute with water to volume, and mix. Assay preparation 2 (where it is represented as being in a single-dose container)—Constitute a container of Ceftazidime for Injection in a volume of water, accurately measured, corresponding to the volume of solvent specified in the labeling. Withdraw all of the withdrawable contents, using a suitable hypodermic needle and syringe, and dilute quantitatively with water to obtain a solution containing about 1 mg of ceftazidime (C22H22N6O7S2) per mL. [Note—Protect this solution from light.] Immediately prior to chromatography, transfer 5.0 mL of this solution to a 50-mL volumetric flask, dilute with water to volume, and mix.
Assay preparation 3 (where the label states the quantity of ceftazidime in a given volume of constituted solution)—Constitute a container of Ceftazidime for Injection in a volume of water, accurately measured, corresponding to the volume of solvent specified in the labeling. Dilute an accurately measured volume of the constituted solution quantitatively with water to obtain a solution containing about 1 mg of ceftazidime (C22H22N6O7S2) per mL. [Note—Protect this solution from light.] Immediately prior to chromatography, transfer 5.0 mL of this solution to a 50-mL volumetric flask, dilute with water to volume, and mix.
Procedure—Proceed as directed for Procedure in the Assay under Ceftazidime. Calculate the percentage of ceftazidime (C22H22N6O7S2) on the dried and sodium carbonate-free or arginine-free basis in the portion of Ceftazidime for Injection taken by the formula:
25,000{C/[W (100 − m − s)]}(rU/rS)
in which C is the concentration, in µg per mL, of ceftazidime (C22H22N6O7S2) in the Standard preparation; W is the quantity, in mg, of Ceftazidime for Injection taken to prepare Assay preparation 1; m is the total percentage of loss on drying; s is the percentage of sodium carbonate or arginine in the Ceftazidime for Injection taken; and rU and rS are the peak responses obtained from the Assay preparation and the
Standard preparation, respectively. Calculate the quantity, in mg, of ceftazidime (C22H22N6O7S2) withdrawn from the container, or in the portion of constituted solution taken by the formula:
(L/D)(C)(rU/rS)
in which L is the labeled quantity, in mg, of ceftazidime (C22H22N6O7S2) in the container, or in the volume of constituted solution taken; and D is the concentration, in µg, of ceftazidime (C22H22N6O7S2) per mL, of Assay preparation 2 or Assay preparation 3, based on the labeled quantity in the container or in the portion of constituted solution taken, respectively, and the extent of dilution.
