Tolcapone Tablets

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

Tolcapone Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of tolcapone (C₁₄H₁₁NO₅).

2 IDENTIFICATION

Change to read:

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

Wavelength range: Between 2200 and 1090 cm⁻¹

Sample: Grind 10 Tablets to a fine powder.

Analysis: Transfer an amount of powder equivalent to 3 mg of tolcapone into a polystyrene vial containing 2 mixing beads. Add 300 mg of IR-grade potassium bromide, and disperse the material in the matrix by agitating the capped vial in a grinding mill for 2 min. Transfer a portion of the material to a sample cup. Record the diffuse reflectance IR spectrum.

Acceptance criteria: The spectrum thus obtained exhibits maxima only at the same wavelengths as those of a similar preparation of USP Tolcapone RS, concomitantly measured.

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

3.1 Procedure

Diluent 1: Methanol and acetonitrile (24:15)

Diluent 2: Acetonitrile, methanol, and water (25:40:35)

Buffer: Transfer 6.8 g of monobasic potassium phosphate into a 1-L volumetric flask. Dissolve in about 980 mL of water. Adjust with phosphoric acid to a pH of 2.0. Dilute with water to volume.

Mobile phase: Acetonitrile, methanol, and Buffer (25:40:35)

System suitability solution: 100 µg/mL of USP Tolcapone RS, 10 µg/mL of USP Tolcapone Related Compound A RS, and 10 µg/mL of USP Tolcapone Related Compound B RS in Diluent 2

Standard stock solution: 1.0 mg/mL of USP Tolcapone RS in Diluent 1

Standard solution: 0.1 mg/mL of USP Tolcapone RS from Standard stock solution prepared as follows. Transfer a suitable volume of Standard stock solution to a suitable volumetric flask. Add 55% of the flask volume of Diluent 1 and dilute with water to volume.

Sample stock solution: Nominally 1.0 mg/mL of tolcapone from NLT 20 Tablets prepared as follows. Finely powder the Tablets and transfer a portion of the powder equivalent to NLT 100 mg of tolcapone to a suitable volumetric flask, add 10% of the flask volume of water, and sonicate for 10 min. Add 65% of the flask volume of Diluent 1, and sonicate for 15 min. Allow the sample to settle. If the material is still undispersed, sonicate for an additional 5 min. Dilute with water to volume, and mix. Centrifuge a portion of this solution.

Sample solution: Nominally 0.1 mg/mL of tolcapone from the centrifuged Sample stock solution prepared as follows. Transfer a suitable volume of the Sample stock solution to a suitable volumetric flask. Dilute with Diluent 2 to volume. Pass a portion of the solution through a filter of 0.45-µm pore size.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 230 nm
• Column: 4.0-mm × 25-cm; 5-µm packing L1
• Flow rate: 1 mL/min
• Injection volume: 20 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times are given in Table 1.]
• Suitability requirements
• Resolution: NLT 4.0 between tolcapone related compound B and tolcapone, System suitability solution
• Tailing factor: NMT 1.5, Standard solution
• Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tolcapone (C₁₄H₁₁NO₅) in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Tolcapone RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of tolcapone in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Medium: pH 6.8 phosphate buffer containing 1% of sodium lauryl sulfate; 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Standard stock solution: 1 mg/mL of USP Tolcapone RS prepared as follows. Transfer a suitable quantity of USP Tolcapone RS to a suitable volumetric flask. Add 10% of the flask volume of methanol. Dissolve and dilute with Medium to volume.

Standard solution: (L/1000) mg/mL of USP Tolcapone RS from a suitable volume of Standard stock solution in Medium, where L is the label claim, in mg/Tablet

Sample solution: Filter portions of the solution under test, suitably diluted with Medium if necessary.

Instrumental conditions

• Mode: UV
• Analytical wavelength: 271 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tolcapone (C₁₄H₁₁NO₅) dissolved:

Result = (Aᵤ/Aₛ) × Cₛ × V × D × (1/L) × 100

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

Cₛ = concentration of USP Tolcapone RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

D = dilution factor if dilution was necessary

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of tolcapone (C₁₄H₁₁NO₅) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉

Meet the requirements

5 IMPURITIES

5.1 Organic Impurities

Diluent 1, Diluent 2, Mobile phase, System suitability solution, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak area of any degradation product in the Sample solution

rₛ = peak area of tolcapone in the Standard solution

Cₛ = concentration of USP Tolcapone RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of the Sample solution (mg/mL)

Acceptance criteria: See Table 1.

Table 1

ᵃ Process impurity, controlled in the drug substance, and included for information only. Not to be included in total degradation products.

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Tolcapone RS

USP Tolcapone Related Compound A RS

4′-Methyl-3,4-dihydroxybenzophenone C₁₄H₁₂O₃ 228.24

USP Tolcapone Related Compound B RS

4-Hydroxy-3-methoxy-4′-methyl-5-nitrobenzophenone C₁₅H₁₃NO₅ 287.27a