Oxacillin 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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C₁₉H₁₈N₃NaO₅S · H O 441.43

4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3,3-dimethyl-6-[[(5-methyl-3-phenyl-4-isoxazolyl)-carbonyl]amino]-7-oxo-, monosodium salt, monohydrate, [2S-(2α,5α,6β)]-;

Monosodium (2S,5R,6R)-3,3-dimethyl-6-(5-methyl-3-phenyl-4-isoxazolecarboxamido)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate monohydrate CAS RN ®: 7240-38-2; UNII: G0V6C994Q5.

Anhydrous

C₁₉H₁₈N₃NaO₅S 423.43 CAS RN ®: 1173-88-2; UNII: 4TWD2995UP.

1 DEFINITION

Oxacillin Sodium contains the equivalent of NLT 815 μg/mg and NMT 950 μg/mg of oxacillin (C₁₉H₁₉N₃O₅S).

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: Meets the requirements

3 ASSAY

Procedure

Protect solutions containing oxacillin from light.

Solution A: 1.18 g/L of sodium 1-hexanesulfonate monohydrate and 0.8 mL/L of ammonium hydroxide in water, adjusted with phosphoric acid to a pH of 2.8–3.2

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Return to the original conditions and re-equilibrate the system.

Diluent: Acetonitrile and water (15:85)

System suitability stock solution: 0.1 mg/mL of USP Oxacillin Related Compound C RS in Diluent. Sonicate as needed to dissolve.

System suitability solution: 0.01 mg/mL of USP Oxacillin Related Compound C RS from System suitability stock solution and 1 mg/mL of USP Oxacillin Sodium RS in Diluent. Store this solution at 4°.

Standard solution: 1 mg/mL of USP Oxacillin Sodium RS in Diluent. Sonicate as needed to dissolve. Store this solution at 4°.

Sample solution: 1 mg/mL of Oxacillin Sodium in Diluent. Sonicate as needed to dissolve. Store this solution at 4°.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Temperatures

Column: 40°

Autosampler: 4°

Flow rate: 1.5 mL/min

Injection volume: 2 μL

System suitability

Samples: System suitability solution and Standard solution

[Note - The relative retention times for oxacillin related compound C and oxacillin are about 0.96 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between oxacillin related compound C and oxacillin, System suitability solution

Tailing factor: 0.8–1.5, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the quantity, in μg/mg, of oxacillin (C₁₉H₁₉N₃O₅S) in the portion of Oxacillin Sodium taken:

Result = (r_U/r_S) × (C_S/C_U) × P

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

P = potency of oxacillin in USP Oxacillin Sodium RS (μg/mg)

Acceptance criteria: 815–950 μg/mg

4 IMPURITIES

Organic Impurities

Protect solutions containing oxacillin from light.

Solution A: 6 g/L of anhydrous monobasic sodium phosphate, 0.56 g/L of sodium 1-hexanesulfonate monohydrate, and 0.05 g/L of edetate disodium. Adjust with phosphoric acid to a pH of 3.0–3.2.

Solution B: Acetonitrile

Mobile phase: See Table 2.

Table 2

Return to the original conditions and re-equilibrate the system.

Diluent: Acetonitrile and water (15:85)

System suitability stock solution: 0.1 mg/mL of USP Oxacillin Related Compound C RS in Diluent. Do not sonicate.

System suitability solution: 0.01 mg/mL of USP Oxacillin Related Compound C RS from System suitability stock solution and 1 mg/mL of USP Oxacillin Sodium RS in Diluent. Store this solution at 4°.

Standard solution: 0.01 mg/mL of USP Oxacillin Sodium RS in Diluent. Do not sonicate. Store this solution at 4°.

Sample solution: 1 mg/mL of Oxacillin Sodium in Diluent. Do not sonicate. Store this solution at 4°.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Temperatures

Column: 22°

Autosampler: 4°

Flow rate: 1.5 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between oxacillin related compound C and oxacillin, System suitability solution

Tailing factor: 0.8–1.5, Standard solution

Relative standard deviation: NMT 2.5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) × (C_S/C_U) × P × (F₁/F₂) × 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 Oxacillin Sodium RS in the Standard solution (mg/mL)

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

P = potency of oxacillin in USP Oxacillin Sodium RS (μg/mg)

F₁ = conversion factor, 0.001 mg/μg

F₂ = relative response factor (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.05%.

Table 3

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

^b(4S)-2-[Carboxy(5-methyl-3-phenylisoxazole-4-carboxamido)methyl]-5,5-dimethylthiazolidine-4-carboxylic acid.

^c The system resolves two isomers. The limit is for the sum of the isomers.

^d(3S,7R)-2,2-Dimethyl-5-(5-methyl-3-phenylisoxazol-4-yl)-2,3,7,7a-tetrahydroimidazo[5,1-b]thiazole-3,7-dicarboxylic acid.

^e(4S)-5,5-Dimethyl-2-[(5-methyl-3-phenylisoxazole-4-carboxamido) methyl]thiazolidine -4- carboxylic acid.

^f (2R,5R,6R)-3,3-Dimethyl-6-(5-methyl-3-phenylisoxazole-4-carboxamido)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carbothioic acid.

^g Isoxazole carboxylic analog; 5-Methyl-3-phenylisoxazole-4-carboxylic acid.

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

ⁱ (2S,5R,6R)-6-{(2S,5R,6R)-3,3-Dimethyl-6-(5-methyl-3-phenylisoxazole-4-carboxamido)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxamido}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid.

^j (2S,5R,6R)-6-{(R)-2-[(2R,4S)-4-Carboxy-5,5-dimethylthiazolidin-2-yl]-2-(5-methyl-3-phenylisoxazole-4-carboxamido)acetamido}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid.

SPECIFIC TESTS

Crystallinity 〈695〉: Meets the requirements

pH 〈791〉

Sample solution: 30 mg/mL

Acceptance criteria: 4.5–7.5

Water Determination, Method I〈921〉: 3.5%–5.0%

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

Bacterial Endotoxins Test 〈85〉: Where the label states that Oxacillin Sodium is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 0.2 USP Endotoxin Units/mg of oxacillin.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, at controlled room temperature.

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 Oxacillin Related Compound C RS

Isoxazole carboxylic analog;

5-Methyl-3-phenylisoxazole-4-carboxylic acid.

C₁₁H₉NO₃ 203.20

USP Oxacillin Sodium RS