Diclofenac Potassium

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 

Diclofenac Potassium contains NLT 99.0% and NMT 101.0% of diclofenac potassium (C₁₄H₁₀Cl₂KNO₂), calculated on the dried basis. 

2 IDENTIFICATION 

2.1 A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K 

2.2 B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U 

Solution: 0.01 mg/mL in Medium 

Medium: Methanol 

Acceptance criteria: Meets the requirements 

Change to read: 

2.3 C. 

Sample solution: Suspend 0.5 g of Diclofenac Potassium in 10 mL of water. Stir and add water until the substance is dissolved. Add 2 mL of 7 N hydrochloric (ERR 1-Sep-2021) acid, stir for 1 h, and lter with the aid of a vacuum. Neutralize with 5 N sodium hydroxide. Analysis: To 1 mL of Sample solution, add 1 mL of 2 N acetic acid and 1 mL of a freshly prepared 100-g/L solution of sodium cobaltinitrite. Acceptance criteria: A yellow or orange yellow precipitate is formed immediately. 

3 ASSAY 

3.1 Procedure 

Sample solution: Dissolve about 300 mg of Diclofenac Potassium in 50 mL of glacial acetic acid. 

Titrimetric system 

(See Titrimetry 〈541〉.) 

Titrant: 0.1 N perchloric acid VS 

Analysis: Titrate with Titrant, determining the endpoint potentiometrically. Perform a blank determination and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 33.424 mg of diclofenac potassium (C₁₄H₁₀Cl₂KNO₂). 

Acceptance criteria: 99.0%–101.0% on the dried basis 

4 IMPURITIES 

4.1 Organic Impurities 

Solution A: 0.01 M phosphoric acid and 0.01 M monobasic sodium phosphate (1:1). If necessary, adjust with additional portions of the appropriate components to a pH of 2.5 ± 0.2. 

Mobile phase: Methanol and Solution A (70:30) 

Diluent: Methanol and water (70:30) 

System suitability solution: 40 µg/mL of diethyl phthalate, 0.5 mg/mL of USP Diclofenac Potassium RS, and 22.5 µg/mL of USP Diclofenac Related Compound A RS in Diluent 

Standard stock solution: 0.25 mg/mL of USP Diclofenac Related Compound A RS in methanol 

Standard solution: 1.5 µg/mL of USP Diclofenac Related Compound A RS in Diluent from Standard stock solution Sample solution: 0.5 mg/mL of Diclofenac Potassium in Diluent 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 25-cm; packing L7 

Flow rate: 1 mL/min 

Injection volume: 30 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times for diethyl phthalate, diclofenac related compound A, and diclofenac are about 0.5, 0.7, and 1.0, respectively.] 

Suitability requirements 

Resolution: NLT 4.0 between diethyl phthalate and diclofenac related compound A, System suitability solution 

Relative standard deviation: NMT 5.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of diclofenac related compound A in the portion of Diclofenac Potassium taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of diclofenac related compound A from the Sample solution 

r_s = peak response of diclofenac related compound A from the Standard solution 

C_s = concentration of USP Diclofenac Related Compound A RS in the Standard solution (µg/mL) 

C_u = concentration of Diclofenac Potassium in the Sample solution (µg/mL) 

Calculate the percentage of each other impurity in the portion of Diclofenac Potassium taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of each individual impurity from the Sample solution 

r_s = peak response of diclofenac related compound A from the Standard solution 

C_s = concentration of USP Diclofenac Related Compound A RS in the Standard solution (µg/mL) 

C_u = concentration of Diclofenac Potassium in the Sample solution (µg/mL) 

Acceptance criteria 

Diclofenac related compound A: NMT 0.1% 

Each other individual impurity: NMT 0.1% 

Total impurities: NMT 0.3% 

5 SPECIFIC TESTS 

5.1 pH 〈791〉 

Sample solution: 1% aqueous solution 

Acceptance criteria: 7.0–8.5 

5.2 Loss on Drying 〈731〉 

Analysis: Dry at 105° under vacuum for 3 h. 

Acceptance criteria: NMT 0.5% 

6 ADDITIONAL REQUIREMENTS 

6.1 Packaging and Storage:

Preserve in light-resistant containers, and store at controlled room temperature. 

6.2 USP Reference Standards 〈11〉 

USP Diclofenac Potassium RS 

USP Diclofenac Related Compound A RS 

N-(2,6-Dichlorophenyl)indolin-2-one. 

C₁₄H₉Cl₂NO           278.14