Dicloxacillin 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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1 DEFINITION 

Dicloxacillin Sodium contains the equivalent of NLT 850 µg/mg of dicloxacillin (C₁₉H₁₇Cl₂N₃O₅S). 

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 

Analysis: Ignite about 100 mg. Proceed as directed in the chapter using a solution (1 in 20) of the residue in acetic acid. Acceptance criteria: Meets the requirements 

3 ASSAY 

3.1 Procedure 

Protect solutions containing dicloxacillin 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 2.9–3.1 

Solution B: Acetonitrile 

Mobile phase: See Table 1. 

Table 1 

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

Diluent: Acetonitrile and water (50:50) 

System suitability stock solution: 0.1 mg/mL of USP Dicloxacillin Related Compound D RS in Diluent. Sonicate as needed to dissolve. System suitability solution: 0.001 mg/mL of USP Dicloxacillin Related Compound D RS from the System suitability stock solution and 0.1 mg/mL of USP Dicloxacillin Sodium RS in Diluent. Store this solution at 4°. 

Standard solution: 0.1 mg/mL of USP Dicloxacillin Sodium RS in Diluent. Sonicate as needed to dissolve. Store this solution at 4°. Sample solution: 0.1 mg/mL of Dicloxacillin 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 

Autosampler: 4° 

Column: 40° 

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 dicloxacillin and dicloxacillin related compound D are about 1.0 and 1.1, respectively.] Suitability requirements 

Resolution: NLT 1.5 between dicloxacillin and dicloxacillin related compound D, 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 dicloxacillin (C₁₉H₁₇Cl₂N₃O₅S) in the portion of Dicloxacillin 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 Dicloxacillin Sodium RS in the Standard solution (mg/mL)

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

P = potency of dicloxacillin in USP Dicloxacillin Sodium RS (µg/mg) 

Acceptance criteria: NLT 850 µg/mg 

4 IMPURITIES 

4.1 Organic Impurities 

Protect solutions containing dicloxacillin from light. 

Solution A, Solution B, Diluent, and Chromatographic system: Proceed as directed in the Assay. 

Mobile phase: See Table 2. 

Table 2 

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

System suitability stock solution: 0.1 mg/mL of USP Dicloxacillin Related Compound D RS in Diluent 

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

Standard solution: 0.01 mg/mL of USP Dicloxacillin Sodium RS in Diluent. Sonicate as needed to dissolve. Store this solution at 4°. Sample solution: 1 mg/mL of Dicloxacillin Sodium in Diluent. Sonicate as needed to dissolve. Store this solution at 4°.

System suitability 

Samples: System suitability solution and Standard solution 

Suitability requirements 

Resolution: NLT 1.5 between dicloxacillin related compound D and dicloxacillin, 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 Dicloxacillin 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 Dicloxacillin Sodium RS in the Standard solution (mg/mL) 

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

P = potency of dicloxacillin in USP Dicloxacillin Sodium RS (µg/mg) 

F₁ = conversion factor, 0.001 mg/µg

F₂ = relative response factor (see Table 3) 

Acceptance criteria 

Individual impurities: NMT 1.0%

Total impurities: NMT 5.0% 

See Table 3 for relative retention times and relative response factors. 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 The system resolves two isomers. 

c (4S)-2-{Carboxy[3-(2,6-dichlorophenyl)-5-methylisoxazole-4-carboxamido]methyl}-5,5-dimethylthiazolidine-4-carboxylic acid.

d [3-(2,6-Dichlorophenyl)-5-methylisoxazole-4-carbonyl]glycine. 

e (2R,4S)-3-Acetyl-2-{(R)-carboxy[3-(2,6-dichlorophenyl)-5-methylisoxazole-4-carboxamido]methyl}-5,5-dimethylthiazolidine-4-carboxylic acid. 

f (4S)-2-{[3-(2,6-Dichlorophenyl)-5-methylisoxazole-4-carboxamido]methyl}-5,5-dimethylthiazolidine-4-carboxylic acid.

g 3-(2,6-Dichlorophenyl)-5-methylisoxazole-4-carboxylic acid. 

h (2S,5R,6R)-6-{(2S,5R,6R)-6-[3-(2,6-Dichlorophenyl)-5-methylisoxazole-4-carboxamido]-3,3-dimethyl-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. 

4.2 Dimethylaniline 〈223〉: Meets the requirements 

5 SPECIFIC TESTS 

5.1 Crystallinity 〈695〉: Meets the requirements 

5.2 pH 〈791〉 

Sample solution: 10 mg/mL in water 

Acceptance criteria: 4.5–7.5 

5.3 Water Determination 〈921〉, Method I: 3.0%–5.0% 

6 ADDITIONAL REQUIREMENTS 

6.1 Packaging and Storage: Preserve in tight containers. 

6.2 USP Reference Standards 〈11〉 

USP Dicloxacillin Sodium RS 

USP Dicloxacillin Related Compound D RS 

3-(2,6-Dichlorophenyl)-5-methylisoxazole-4-carboxylic acid. 

C₁₁H₇Cl₂NO₃            272.08