Ceftriaxone Sodium

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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C₁₈H₁₆N₈Na₂O₇S₃  · 3½H O 661.60 

5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid,7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[[(1,2,5,6-tetrahydro-2- methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-, disodium salt, [6R-[6α,7β(Z)]]-, hydrate, (2:7); 

(6R,7R)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-as-triazin-3-yl)thio]methyl]-5-thia-1- azabicyclo[4.2.0]-oct-2-ene-2-carboxylic acid, 72-(Z)-(O-methyloxime), disodium salt, hemiseptahydrate CAS RN®: 104376-79-6; UNII:  

023Z5BR09K. 

Anhydrous 598.56 

1 DEFINITION 

Ceftriaxone Sodium contains the equivalent of NLT 795 µg/mg of ceftriaxone (C₁₈H₁₈N₈O₇S₃), calculated on the anhydrous basis.

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. C. Identification Tests—General 〈191〉, Sodium 

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 to a pH of 5.0 prior to nal 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 of USP Ceftriaxone Sodium RS and 50 µg/mL of 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: 0.3 mg/mL of Ceftriaxone Sodium in Mobile phase 

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 and Sample solution 

Calculate the quantity, in µg/mg, of ceftriaxone (C₁₈H₁₈N₈O₇S₃) in the portion of Ceftriaxone Sodium 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 795 µg/mg on the anhydrous basis 

4 IMPURITIES 

Organic Impurities 

Protect solutions containing ceftriaxone sodium from light. 

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

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

System suitability 

Samples: System suitability solution and Standard 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 E-isomer and ceftriaxone peaks, System suitability solution 

Signal-to-noise ratio: NLT 10, Standard solution 

Analysis 

Samples: Sample solution and Standard solution 

Calculate the percentage of each individual impurity in the portion of Ceftriaxone Sodium 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 = concentration of Ceftriaxone Sodium 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 7-ACA; (6R,7R)-3-(Acetoxymethyl)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. 

^c To be reported if present in the impurity prole. 

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

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

^f (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. 

^g(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. 

^h(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. 

5 SPECIFIC TESTS 

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% 

Sterility Tests 〈71〉, Test for Sterility of the Product to Be Examined, Membrane Filtration: Where the label states that it is sterile, it meets the requirements. 

Bacterial Endotoxins Test 〈85〉: Where the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 0.20 USP Endotoxin Units/mg of ceftriaxone. 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers, protected from light. 

Labeling: Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms. 

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