Entacapone

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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(E)-α-Cyano-N,N-diethyl-3,4-dihydroxy-5-nitrocinnamamide;

2-Propenamide, 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-,(E)- CAS RN^®: 130929-57-6; UNII: 4975G9NM6T.

1 DEFINITION

Entacapone contains NLT 98.0% and NMT 102.0% of C₁₄H₁₅N₃O₅, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K 

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Buffer: 2.34 g/L of monobasic sodium phosphate dihydrate. Adjust with phosphoric acid to a pH of 2.1.

Diluent: Methanol and tetrahydrofuran (7:3)

Mobile phase: Methanol, tetrahydrofuran, and Buffer (22:1:27)

System suitability solution: 1 µg/mL each of USP Entacapone Related Compound A RS and USP Entacapone RS in Diluent

Standard solution: 0.1 mg/mL of USP Entacapone RS in Diluent

Sample solution: 0.1 mg/ml. of Entacapone in Diluent

Chromatographic system

(See Chromatography (621), System Suitability,)

Mode: LC

Detector: UV 300 nm

Column: 4.6-mm × 25-cm; 5-μm packing L11

Flow rate: 1 ml/min

Injection size: 10 μL

System suitability

Samples: System suitability solution and Standard solution

Note-The relative retention times for entacapone related compound A and entacapone are 0.8 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between entacapone related compound A and entacapone, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₄H₁₅N₃O₅, in the portion of Entacapone taken:

Result = (r_U/(r_S) × (C_S /C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 98.0%-702:0% on the dried basis

4 IMPURITIES

Inorganic Impurities

Residue on Ignition (281): NMT 0.1%

Organic Impurities

Procedure

Buffer, Diluent, and Mobile phase: Proceed as directed in the Assay.

Standard solution: the the System stability solution prepared as directed in the Assay

Sample solution: 1.0 mg/ml of Entacapone in Diluent

Chromatographic system: Prepare ac directed in the Assay

Run time: 2 times the retention bime of the entacapone peak

System sullability

Sample: Standard solution

Suitability requirements

Resolution: NIT 2.0 between entacapone nelisted compound A and entacapone

Relative standard deviation NMT 10.0% based on the entacapone peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Entacapone taken

Result = (r_U/(r_S) × (C_S /C_U) x 100

r_U = peak response of any impurity from the Sample solution

r_S = peak response of entacapone from the Standard solution

C_S = concentration of USP Entacapone RS in the Standart solution (mg/ml)

C_U = concentration of Entacapone in the Sample solution (mg/ml)

Acceptance criteria

Individual impurities: See vrourity Tablet 1

Total impurities: NMT 0.2%

[[Note-Do not include entacapone related compound A in the calculation of total impurities]

^a (Z)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylacrylamide.

5 SPECIFIC TESTS

Loss on Drying (731)

Analysis: Dry 1.0 g of the sample in vacuum at a pressure not exceeding 49 mm of mercury at 65" to constant weight.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKARD STORAGE: Preserve in tight containers, and store at room temperature.