Sulbactam Sodium

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

Change to read:

C₈H₁₀NNaO₅S 255.22

4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-, 4,4-dioxide, sodium salt, (2S-cis)-;

Sodium (2S,5R)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 4,4-dioxide CAS RN®: 69388-84-7; UNII: DKQ4T82YE6.

Sulbactam (free acid)

C₈H₁₁NO₅S 233.24 CAS RN®: 68373-14-8; UNII: S4TF6I2330. (USP 1-Dec-2023)

1 DEFINITION

Sulbactam Sodium contains NLT 886 and NMT 941 μg/mg of sulbactam (C₈H₁₁NO₅S), calculated on the anhydrous basis.

2 IDENTIFICATION

Add the following:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (USP 1-Dec-2023)

Change to read:

B. (USP 1-Dec-2023) The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Change to read:

C. (USP 1-Dec-2023) Identification Tests—General 〈191〉, Chemical Identification Tests, Sodium: Meets the requirements

3 ASSAY

Procedure

Buffer solution: 2.7 g/L of monobasic potassium phosphate, adjusted with dilute phosphoric acid to a pH of 4.0

Solution A: 5.4 g/L of monobasic potassium phosphate, adjusted with dilute phosphoric acid to a pH of 4.0

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Standard solution: 0.7 mg/mL of USP Sulbactam RS prepared as follows. Dissolve a suitable amount of USP Sulbactam RS in acetonitrile, using 2% of the final volume, and dilute with Buffer solution to volume.

Sample solution: 0.77 mg/mL of Sulbactam Sodium prepared as follows. Dissolve a suitable amount of Sulbactam Sodium in acetonitrile, using 2% of the final volume, and dilute with Buffer solution to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4-mm × 15-cm; 3-μm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the quantity, in μg, of sulbactam (C₈H₁₁NO₅S) in each mg of Sulbactam Sodium taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = concentration of Sulbactam Sodium in the Sample solution (mg/mL)

P = potency of sulbactam in USP Sulbactam RS (mg/mg)

F = conversion factor, 1000 μg/mg

Acceptance criteria: 886–941 μg/mg on the anhydrous basis

4 IMPURITIES

Change to read:

Organic Impurities

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

Diluent: 2 mL of acetonitrile diluted with Buffer solution to 100 mL

System suitability solution: 0.7 μg/mL each of USP Sulbactam Related Compound A RS, USP Sulbactam Related Compound D RS, USP

Sulbactam Related Compound E RS, and USP Sulbactam Related Compound F RS, prepared as follows. Dissolve suitable amounts of USP

Sulbactam Related Compound A RS, USP Sulbactam Related Compound D RS, USP Sulbactam Related Compound E RS, and USP

Sulbactam Related Compound F RS in acetonitrile using 10% of the

nal volume, and sonicate as needed. Dilute with Diluent to volume.

Protect this solution from light.

Standard stock solution: 0.7 mg/mL of USP Sulbactam RS prepared as follows. Dissolve a suitable amount of USP Sulbactam RS in acetonitrile, using 2% of the final volume, and dilute with Buffer solution to volume.

Standard solution: 0.7 μg/mL of USP Sulbactam RS from the Standard stock solution, in Diluent

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between sulbactam related compound D and sulbactam related compound E, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each impurity in the portion of Sulbactam Sodium taken:

Result = (r_U/r_S) × (C_S/C_U) × P × (1/F) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response from the Standard solution

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

C_U = concentration of Sulbactam Sodium in the Sample solution (mg/mL)

P = potency of sulbactam in USP Sulbactam RS (mg/mg)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

^a 3-Sulfino-d-valine; (2S)-2-Amino-3-methyl-3-sulfinobutanoic acid.

^b (USP 1-Dec-2023) (2S,5R,6R)-6-Amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid.

^c (2S,5R,6R)-6-Bromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 4,4-dioxide.

d 6-Bromopenicillanic acid; (2S,5R,6R)-6-Bromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid.

^e 6,6-Dibromopenicillanic acid sulfone; also known as (2S,5R)-6,6-Dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2- carboxylic acid 4,4-dioxide.

^f 6,6-Dibromopenicillanic acid; also known as (2S,5R)-6,6-Dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid.

5 SPECIFIC TESTS

Crystallinity 〈695〉: Meets the requirements

Change to read:

Bacterial Endotoxins Test 〈85〉: Where the label states that Sulbactam Sodium is sterile or must be subjected to further processing during the preparation of injectable dosage forms, the level of bacterial endotoxins is such that the requirement under the relevant dosage form monograph(s) in which Sulbactam Sodium is used can be met. (USP 1-Dec-2023)

Change to read:

Sterility Tests 〈71〉: Where the label states that Sulbactam Sodium is sterile, it meets the requirements.

(USP 1-Dec-2023)

Water Determination 〈921〉, Method I: NMT 1.0%

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.

Change to read:

USP Reference Standards 〈11〉

USP Sulbactam RS

USP Sulbactam Sodium RS (USP 1-Dec-2023)

USP Sulbactam Related Compound A RS

(2S)-2-Amino-3-methyl-3-sulfinobutanoic acid.

C₅H₁₁NO₄S 181.21

USP Sulbactam Related Compound D RS

(2S,5R,6R)-6-Bromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, potassium salt.

C₈H₉BrKNO₃S 318.23

USP Sulbactam Related Compound E RS

(2S,5R)-6,6-Dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 4,4-dioxide.

C₈H₉Br₂NO₅S 391.03

USP Sulbactam Related Compound F RS

(2S,5R)-6,6-Dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid.

C₈H₉Br₂NO₃S 359.03