Aztreonam for Injection
» Aztreonam for Injection is a dry mixture of sterile Aztreonam and Arginine. It contains not less than 90.0 percent and not more than 105.0 percent of aztreonam (C13H17N5O8S2), calculated on the anhydrous and arginine-free basis. Each container contains not less than 90.0 percent and not more than 120.0 percent of the labeled amount of aztreonam (C13H17N5O8S2).
Packaging and storage— Preserve in Containers for Sterile Solids as described under Injections 1.
Constituted solution— At the time of use, it meets the requirements for Constituted Solutions under Injections 1.
Identification— The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those of the Standard preparation, as obtained in the Assay.
Bacterial endotoxins 85— It contains not more than 0.17 USP Endotoxin Unit per mg of aztreonam.
Sterility 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 4.5 and 7.5, in a solution containing 100 mg of aztreonam per mL.
Water, Method I 921: not more than 2.0%.
Particulate matter 788: meets the requirements for small-volume injections.
Content of arginine—
Mobile phase, Standard preparation, Resolution solution, and Chromatographic system— Proceed as directed in the Assay.
Test preparation— Use Assay preparation 1, prepared as directed in the Assay.
Procedure— Proceed as directed in the Assay. Calculate the percentage of arginine (C6H14N4O2) in the Aztreonam for Injection taken by the formula:
100(CS / CU)(rU / rS)
in which CS is the concentration, in mg per mL, of USP l-Arginine RS in the Standard preparation; CU is the concentration, in mg per mL, of Aztreonam for Injection in Assay preparation 1, based on the weight, in mg, of Aztreonam for Injection removed from the container 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 under Injections 1.
Assay—
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 suitable 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 Aztreonam RS and USP l-Arginine RS quantitatively in Mobile phase to obtain a solution containing known concentrations of about 0.2 mg of each 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 Open Ring Aztreonam RS.
Assay preparation 1— Weigh accurately 1 container of Aztreonam for Injection. Transfer the contents of the container to a 100-mL volumetric flask. Weigh the empty container, and calculate the weight, in mg, of Aztreonam for Injection removed. Dissolve the powder in the volumetric flask in Mobile phase, dilute with Mobile phase to volume, and mix. Dilute an accurately measured volume of this solution quantitatively with Mobile phase to obtain a solution having a concentration of about 0.2 mg of aztreonam per mL.
Assay preparation 2— Constitute 1 container of Aztreonam for Injection with a volume of water, accurately measured, corresponding to the volume of solvent specified in the labeling, except where the capacity of the container is 100 mL or greater to constitute with 10 mL of water. Withdraw the total withdrawable contents of the container, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution containing about 0.2 mg of aztreonam per mL.
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 206-nm detector, a 4.6-mm × 50-cm saturator precolumn 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 Resolution solution, and record the responses as directed for Procedure: the relative retention times are about 0.8 for aztreonam and 1.0 for open ring aztreonam; the resolution, R, between aztreonam and open ring aztreonam 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, Assay preparation 1, and Assay preparation 2 into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.3 for aztreonam and 1.0 for arginine. Calculate the percentage of aztreonam (C13H17N5O8S2) in the Aztreonam for Injection taken by the formula:
0.1(CS PS / CU)(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; CU is the concentration, in mg per mL, of Aztreonam for Injection in Assay preparation 1, based on the weight, in mg, of Aztreonam for Injection removed from the container and the extent of dilution; and rU and rS are the aztreonam peak responses obtained from Assay preparation 1 and the Standard preparation, respectively. Calculate the quantity, in mg, of aztreonam (C13H17N5O8S2) in the container of Aztreonam for Injection used to prepare Assay preparation 2 taken by the formula:
(CS PS L / 1000CU)(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; L is the labeled quantity, in mg, of aztreonam in the container of Aztreonam for Injection; CU is the concentration, in mg per mL, of aztreonam in Assay preparation 2, on the basis of the labeled quantity, in mg, of aztreonam in the container and the extent of dilution; and rU and rS are the aztreonam peak responses obtained from Assay preparation 2 and the Standard preparation, respectively.
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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 1617
Pharmacopeial Forum: Volume No. 34(4) Page 906
Chromatographic Column—
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.