Ceftriaxone for Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION 

Ceftriaxone for Injection contains an amount of Ceftriaxone Sodium equivalent to NLT 776 µg/mg of ceftriaxone (C₁₈H₁₈N₈O₇S₃), calculated on the anhydrous basis, and the equivalent of NLT 90.0% and NMT 115.0% of the labeled amount of ceftriaxone (C₁₈H₁₈N₈O₇S₃).  

2 IDENTIFICATION 

Change to read: 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020) 

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

3 ASSAY 

Procedure 

Protect solutions containing ceftriaxone sodium from light. 

Solution A: 9 g/L of monobasic potassium phosphate in water 

Solution B: 24 g/L of dibasic sodium phosphate, dodecahydrate in water 

Solution C: 20 g/L of citric acid in water. Adjust with 10 N sodium hydroxide TS to a pH of 5.0 prior to dilution. 

Buffer: Combine 389 mL of Solution A and 611 mL of Solution B. Adjust with 10 N sodium hydroxide TS or phosphoric acid to a pH of 7.0. Mobile phase: Dissolve 2.0 g each of tetradecylammonium bromide and tetraheptylammonium bromide in a mixture of 440 mL of water, 55 mL of Buffer, 5.0 mL of Solution C, and 500 mL of acetonitrile. 

System suitability solution: 50 µg/mL each of USP Ceftriaxone Sodium RS and USP Ceftriaxone Sodium E-Isomer RS in Mobile phase Standard solution: 0.3 mg/mL of USP Ceftriaxone Sodium RS in Mobile phase 

Sample solution 1: Nominally 0.3 mg/mL of ceftriaxone from Ceftriaxone for Injection in Mobile phase 

Sample solution 2 (where it is represented as being in a single-dose container): Nominally 0.3 mg/mL of ceftriaxone in Mobile phase prepared as follows. Constitute Ceftriaxone for Injection in a volume of water corresponding to the volume of solvent specied in the labeling. Withdraw all of the withdrawable contents using a suitable hypodermic needle and syringe, and transfer to a suitable volumetric ask. Dilute with Mobile phase to volume. 

Sample solution 3 (where the label states the quantity of ceftriaxone in a given volume of constituted solution): Nominally 0.3 mg/mL of ceftriaxone in Mobile phase prepared as follows. Constitute Ceftriaxone for Injection in a volume of water corresponding to the volume of solvent specied in the labeling, and dilute with Mobile phase to nal volume. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L1 

Flow rate: 1.5 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times for ceftriaxone and ceftriaxone E-isomer are 1.0 and 1.4, respectively.] 

Suitability requirements 

Resolution: NLT 3.0 between the ceftriaxone and ceftriaxone E-isomer peaks, System suitability solution 

Tailing factor: NMT 2, Standard solution 

Relative standard deviation: NMT 0.7%, Standard solution 

Analysis 

Samples: Standard solution, Sample solution 1, and Sample solution 2 or Sample solution 3 

Calculate the quantity, in µg/mg, of ceftriaxone (C₁₈H₁₈N₈O₇S₃) in the portion of Ceftriaxone for Injection taken: 

Result = (r_U/r_S) × (C_S/C_U) × P 

r_U = peak response of ceftriaxone from Sample solution 1

r_S = peak response of ceftriaxone from the Standard solution

C_S = concentration of USP Ceftriaxone Sodium RS in the Standard solution (mg/mL)

C_U = nominal concentration of ceftriaxone in the Sample solution (mg/mL) 

P = potency of ceftriaxone in USP Ceftriaxone Sodium RS (µg/mg) 

Acceptance criteria: NLT 776 µg/mg on the anhydrous basis 

Calculate the percentage of the labeled amount of ceftriaxone (C₁₈H₁₈N₈O₇S₃) in the portion of Ceftriaxone for Injection withdrawn from the  container or in the portion of the constituted solution: 

Result = (r_U/r_S) × (C_S/C_U) × P × F × 100 

r_U = peak response of ceftriaxone from Sample solution 2 or Sample solution 3

r_S = peak response of ceftriaxone from the Standard solution 

C_S = concentration of USP Ceftriaxone Sodium RS in the Standard solution (mg/mL) 

C_U = nominal concentration of ceftriaxone in Sample solution 2 or Sample solution 3 (mg/mL)

P = potency of ceftriaxone in USP Ceftriaxone Sodium RS (µg/mg) 

F = conversion factor, 0.001 mg/µg 

Acceptance criteria: 90.0%–115.0% of the labeled amount of ceftriaxone 

4 PERFORMANCE TESTS 

Uniformity of Dosage Units 〈905〉: Meets the requirements 

5 IMPURITIES 

Organic Impurities 

Protect solutions containing ceftriaxone sodium from light. 

Solution A, Solution B, Solution C, Buffer, Mobile phase, System suitability solution, and Chromatographic system: Proceed as directed in the Assay. 

Standard solution: 3 µg/mL of USP Ceftriaxone Sodium RS in Mobile phase 

Sample solution: Nominally 0.3 mg/mL of ceftriaxone from Ceftriaxone for Injection in Mobile phase 

System suitability 

Sample: System suitability solution 

[Note—The relative retention times for ceftriaxone and ceftriaxone E-isomer are listed in Table 1.] 

Suitability requirements 

Resolution: NLT 3.0 between the ceftriaxone and ceftriaxone E-isomer 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each individual impurity in the portion of Ceftriaxone for Injection taken: 

Result = (r_U/r_S) × (C_S/C_U) × P × F × 100 

r_U = peak response of each individual impurity from the Sample solution 

r_S = peak response of ceftriaxone from the Standard solution 

C_S = concentration of USP Ceftriaxone Sodium RS in the Standard solution (mg/mL) 

C_U = nominal concentration of ceftriaxone in the Sample solution (mg/mL) 

P = potency of ceftriaxone in USP Ceftriaxone Sodium RS (µg/mg) 

F = conversion factor, 0.001 mg/µg 

Acceptance criteria: See Table 1. Disregard any peak below 0.1%. 

Table 1 

^a(Z)-2-(2-Aminothiazol-4-yl)-N-{(5aR,6R)-1,7-dioxo-1,3,4,5a,6,7-hexahydroazeto[2,1-b]furo[3,4-d][1,3]thiazin-6-yl}-2-(methoxyimino)acetamide. 

^b Process impurities that are controlled in the drug substance are not to be reported, are not included in total impurities, and are listed here for information only. 

^c 3-Mercapto-2-methyl-1,2-dihydro-1,2,4-triazine-5,6-dione. 

^d(Z)-S-Benzothiazol-2-yl 2-(2-aminothiazol-4-yl)-2-(methoxyimino)thioacetate. 

^e(6R,7R)-7-Amino-3-{[(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid. 

^f (6R,7R)-7-[(Z)-2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-{[(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3- yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid. 

^g(6R,7R)-7-[(E)-2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-{[(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3- yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. 

6 SPECIFIC TESTS 

Constituted Solution: At the time of use, it meets the requirements for Injections and Implanted Drug Products 〈1〉, Product Quality Tests Common to Parenteral Dosage Forms, Specic Tests, Completeness and clarity of solutions. 

Bacterial Endotoxins Test 〈85〉: NMT 0.20 USP Endotoxin Units/mg of ceftriaxone 

Sterility Tests 〈71〉, Test for Sterility of the Product to Be Examined, Membrane Filtration: It meets the requirements. Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections 

Crystallinity 〈695〉: Meets the requirements 

pH 〈791〉 

Sample solution: 100 mg/mL 

Acceptance criteria: 6.0–8.0 

Water Determination 〈921〉, Method I: 8.0%–11.0% 

Other Requirements: It meets the requirements for Labeling 〈7〉, Labels and Labeling for Injectable Products. 

7 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for constitution, and protected from light. 

USP Reference Standards 〈11〉 

USP Ceftriaxone Sodium RS 

USP Ceftriaxone Sodium E-Isomer RS 

(6R,7R)-7-[(E)-2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido]-3-{[(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)thio]methyl}-8- oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, disodium salt. 

C₁₈H₁₆N₈Na₂O₇S₃ 598.53