Aztreonam
435.43Propanoic acid, 2-[[[1-(2-amino-4-thiazolyl)-2-[(2-methyl-4-oxo-1-sulfo-3-azetidinyl)amino]-2-oxoethylidene]amino]oxy]-2-methyl-, [2S-[2
,3
(Z)]]-.
(Z)-2-[[[(2-Amino-4-thiazolyl)[[(2S,3S)-2-methyl-4-oxo-1-sulfo-3-azetidinyl]carbamoyl]methylene]amino]oxy]-2-methylpropionic acid
[78110-38-0].» Aztreonam is anhydrous or hydrated. The anhydrous form contains not less than 90.0 percent and not more than 105.0 percent of C13H17N5O8S2, calculated on the as-is basis. The hydrated form contains not less than 92.0 percent and not more than 105.0 percent of C13H17N5O8S2, calculated on the anhydrous basis.
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.
Identification, Infrared Absorption 
197K
—
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 minutes at room temperature.] Evaporate the solutions to dryness under vacuum, and dry at 40
for 4 hours under vacuum. Perform the test on the residues.
197K—
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 minutes at room temperature.] Evaporate the solutions to dryness under vacuum, and dry at 40 for 4 hours under vacuum. Perform the test on the residues.
Bacterial endotoxins 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 not more than 0.17 USP Endotoxin Unit per mg of aztreonam.
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 not more than 0.17 USP Endotoxin Unit per mg of aztreonam.
Sterility 71—
Where the label states that Aztreonam is sterile, it meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined, using Fluid A to which 23.4 g of sterile arginine has been added to each 1000 mL.
71—
Where the label states that Aztreonam is sterile, it meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined, using Fluid A to which 23.4 g of sterile arginine has been added to each 1000 mL.
Water, Method I 921:
not more than 2.0%. If labeled as the hydrated form: between 12.0% and 18.0%. [note—For this monograph, the term “hydrated form” refers to the -form of Aztreonam which is not a stoichiometric hydrate.]
921:
not more than 2.0%. If labeled as the hydrated form: between 12.0% and 18.0%. [note—For this monograph, the term “hydrated form” refers to the -form of Aztreonam which is not a stoichiometric hydrate.]
Residue on ignition 281:
not more than 0.1%, the charred residue being moistened with 2 mL of nitric acid and 5 drops of sulfuric acid.
281:
not more than 0.1%, the charred residue being moistened with 2 mL of nitric acid and 5 drops of sulfuric acid.
Heavy metals, Method II 231:
0.003%.
231:
0.003%.
Assay—
Mobile phase—
Dissolve 6.8 g of monobasic potassium phosphate in water to make 1000 mL, and adjust with 1 M phosphoric acid to a pH of 3.0 ± 0.1. Prepare a suitable mixture of this solution and methanol (4:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard preparation—
Quantitatively dissolve an accurately weighed quantity of USP Aztreonam RS in Mobile phase to obtain a solution having a known concentration of about 1 mg per mL.
Resolution solution—
Prepare a solution in Mobile phase containing in each mL about 0.2 mg each of USP Aztreonam RS and USP Aztreonam E-Isomer RS.
Assay preparation—
Transfer about 25 mg of Aztreonam, accurately weighed, to a 25-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Chromatographic system
(see Chromatography 621)—The liquid chromatograph is equipped with a 270-nm detector, a 2-mm × 10-cm precolumn containing packing L2, and a 4.6-mm × 30-cm analytical column containing packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.6 for aztreonam and 1.0 for aztreonam E-isomer; the resolution, R, between aztreonam and aztreonam E-isomer is not less than 2.0; the column efficiency as determined from the aztreonam peak is not less than 1000 theoretical plates; the tailing factor for the aztreonam peak is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
621)—The liquid chromatograph is equipped with a 270-nm detector, a 2-mm × 10-cm precolumn containing packing L2, and a 4.6-mm × 30-cm analytical column containing packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.6 for aztreonam and 1.0 for aztreonam E-isomer; the resolution, R, between aztreonam and aztreonam E-isomer is not less than 2.0; the column efficiency as determined from the aztreonam peak is not less than 1000 theoretical plates; the tailing factor for the aztreonam peak is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of C13H17N5O8S2 in the portion of Aztreonam taken by the formula:
2.5(CSPS / W)(rU / rS)
in which CS is the concentration, in mg per mL, of USP Aztreonam RS in the Standard preparation; PS is the assigned purity, in µg per mg, of USP Aztreonam RS; W is the weight, in mg, of Aztreonam taken to prepare the Assay preparation; and rU and rS are the aztreonam peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
Chromatographic Column—
| Topic/Question | Contact | Expert Committee |
| Monograph | Ahalya Wise, M.S.
Scientist 1-301-816-8161 |
(MDANT05) Monograph Development-Antibiotics |
| Reference Standards | Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org |
|
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Senior Scientist 1-301-816-8339 |
(MSA05) Microbiology and Sterility Assurance |
| 71 |
Radhakrishna S Tirumalai, Ph.D.
Senior Scientist 1-301-816-8339 |
(MSA05) Microbiology and Sterility Assurance |
USP32–NF27 Page 1616
Pharmacopeial Forum: Volume No. 33(5) Page 872
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.