Aztreonam

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

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

DOWNLOAD PDF HERE

C₁₃H₁₇N₅O₈S₂           435.43

Propanoic acid, 2-[[[1-(2-amino-4-thiazolyl)-2-[(2-methyl-4-oxo-1-sulfo-3-azetidinyl)amino]-2-oxoethylidene]amino]oxy]-2-methyl-, [2S-[2α,3β(Z)]]-;(Z)-2-({[(2-Amino-4-thiazolyl){[(2S,3S)-2-methyl-4-oxo-1-sulfo-3-azetidinyl]carbamoyl}methylene]amino}oxy)-2-methylpropionic acid CAS RN: 78110-38-0; UNII: G2B4VE5GH8.

1 DEFINITION

Aztreonam, which may be anhydrous or hydrated, contains NLT 92.0% and NMT 105.0% of aztreonam (C₁₃H₁₇N₅O₈S₂), calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

Change to read:
A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{(CN 1-MAY-2020)}: If a difference appears in the IR spectra of the analyte and the standard, dissolve equal portions of the test specimen and the Reference Standard in equal volumes of methanol. [NOTE-TO achieve a complete dissolution, it is suggested to use about 25 ml of methanol for each 50 mg of material, and stir the mixture for 40 min at room temperature.]

Evaporate the solutions to dryness under vacuum, and dry at 40 for 4 h under vacuum. Perform the test on the residues.

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

[NOTE-Store the System suitability solution, Standard solution, and Sample solution at 5^o, and protect from light to prevent isomerization of aztreonam Z-isomer to aztreonam E-isomer.]

Buffer: 6.8 mg/mL of monobasic potassium phosphate in water. Adjust with 1 M phosphoric acid to a pH of 3.0.

Mobile phase: Methanol and Buffer (1:4)

System suitability solution: 1 mg/mL of USP Aztreonam RS and 1 mg/mL of USP Aztreonam E-Isomer RS in Mobile phase

Standard solution: 1 mg/ml. of USP Aztreonam RS in Mobile phase

Sample solution: 1 mg/mL of Aztreonam in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm x 30-cm; 10-µm packing 11

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for aztreonam and aztreonam E-isomer are 1.0 and 1.8, respectively.]

Suitability requirements

Resolution: NLT 2.0 between aztreonam and aztreonam E-isomer, System suitability solution

Tailing factor: NMT 2 for aztreonam, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of aztreonam (C₁₃H₁₇N₅O₈S₂) in the portion of Aztreonam taken:

Result = (r_u /r_s ) × (C_s /C_u ) × P × F × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

C_s = concentration of USP Aztreonam RS in the Standard solution (mg/mL)

C_u = concentration of Aztreonam in the Sample solution (mg/mL)

P = potency of USP Aztreonam RS (µg/mg)

F = unit conversion factor, 0.001 mg/µg

Acceptance criteria: 92.0%–105.0% on the anhydrous and solvent-free basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%, the charred residue being moistened with 2 mL of nitric acid and 5 drops of sulfuric acid

ORGANIC IMPURITIES

[NOTE-Store the System suitability solution, Standard solution, and Sample solution at 5", and protect from light to prevent isomerization of aztreonam Z-isomer to aztreonam E-isomer.]

Mobile phase, System suitability solution, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay..

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Aztreonam taken:

Result = (r_u /r_s ) × (C_s /C_u ) × P × F × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of aztreonam from the Standard solution

C_s = concentration of USP Aztreonam RS in the Standard solution (mg/mL)

C_u = concentration of Aztreonam in the Sample solution (mg/mL)

P = potency of USP Aztreonam RS (µg/mg)

F = unit conversion factor, 0.001 mg/µg

Acceptance criteria: See Table 1.

Table 1

^a (2S,3S)-2-{(Z)-2-[2-Aminothiazol-4-yl]-2-[2-carboxypropan-2-yloxyimino]acetamido}-3-(sulfoamino)butanoic acid.

^b (2S,3S)-3-Amino-2-{(Z)-2-[2-aminothiazol-4-yl]-2-[2-carboxypropan-2-yloxyimino]acetamido}butanoic acid.

^c Open-ring aztreonam and open-ring desulfated aztreonam coelute. The limit is for the sum of these two impurities.

^d (Z)-2-({[(2-Amino-4-thiazolyl){[(2S,3S)-2-methyl-4-oxo-3-azetidinyl]carbamoyl}methylene]amino}oxy)-2-methylpropionic acid.

^e (E)-2-({[(2-Amino-4-thiazolyl){[(2S,3S)-2-methyl-4-oxo-1-sulfo-3-azetidinyl]carbamoyl}methylene]amino}oxy)-2-methylpropionic acid.

^f Ethyl (Z)-2-({[(2-amino-4-thiazolyl){[(2S,3S)-2-methyl-4-oxo-1-sulfo-3-azetidinyl]carbamoyl}methylene]amino}oxy)-2-methylpropionate.

5 SPECIFIC TESTS

STERILITY TESTS (71), Test for Sterility of the Product to Be Examined, Membrane Filtration: Where the label states that Aztreonam is sterile, it meets the requirements using Fluid A, to which 23.4 g of sterile Arginine has been added to each 1000 ml..

WATER DETERMINATION (921), Method /: NMT 2.0%; if labeled as the hydrated form: 12.0%~18.0%. (NOTE-The term "hydrated form" refers to the a form of Aztreonam, which is not a stoichiometric hydrate.]

BACTERIAL ENDOTOXINS TEST (85): Where the label states that Aztreonam is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 0.17 USP Endotoxin Units/mg of aztreonam.

LIMIT OF ALCOHOL

[NOTE-This test is to be performed if alcohol is used while manufacturing Aztreonam.]

Standard solution: 0.004 mL/mL of alcohol from USP Alcohol Determination+Alcohol RS and 0.004 mL/mL of acetonitrile from USP Alcohol

Determination-Acetonitrile RS in dimethylformamide. [NOTE-The Standard solution contains 0.4% alcohol and 0.4% acetonitrile.]

Sample solution: 80 mg/mL of Aztreonam and 0.004 mL/mL of acetonitrile in dimethylformamide. [NOTE-Dissolve Aztreonam in dimethylformamide using 20% of the final volume. Add a suitable aliquot of USP Alcohol Determination-Acetonitrile RS, and dilute with dimethylformamide to volume. The concentration of acetonitrile in the Sample solution is 0.4%.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 3.53 - mm x 30 - m phase G43

Film thickness: 3.0 µm

Temperatures

Injector: 210°

Detector: 280°

Column: See Table 2.

Table 2

Carrier gas: Helium

Linear velocity: 35 cm/s

Injection mode: Split

Injection volume: 0.5 µL

Injection type: Split ratio, 5:1

System suitability

Sample: Standard solution

[Note—The relative retention times for alcohol and acetonitrile are 1.0 and 1.3, respectively.]

Suitability requirements

Resolution: NLT 2.0 between alcohol and acetonitrile

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of alcohol in the portion of Aztreonam taken:

Result = (R_u /R_s ) × [C_s × (D/C_u )] × F × 100

R_s = peak response ratio of alcohol to acetonitrile from the Sample solution

R_s = peak response ratio of alcohol to acetonitrile from the Standard solution

C_s = concentration of alcohol in the Standard solution (mL/mL)

D = density of alcohol (g/mL)

C_u = concentration of Aztreonam in the Sample solution (mg/mL)

F = unit conversion factor, 1000 mg/g

Acceptance criteria: NMT 4%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

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. Where it is the hydrated form, the label so indicates.

USP REFERENCE STANDARDS (11)

USP Alcohol Determination-Acetonitrile RS                C₂H₃N              41.05

USP Alcohol Determinationt Alcohol RS                C₂H₅OH          46.07

USP Aztreonam RS

USP Aztreonam E-lsomer RS

(E)-2-({[(2-Amino-4-thiazolyl){[(2S,3S)-2-methyl-4-oxo-1-sulfo-3-azetidinyl carbamoyl methylene]amino}oxy)-2-methylpropionic acid.

C₁₃H₁₇N₅O₈S₂       435.43