Pirfenidone

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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C₁₂H₁₁NO 185.23

2(1H)-Pyridinone, 5-methyl-1-phenyl-;

5-Methyl-1-phenyl-2(1H)-pyridone CAS RN®: 53179-13-8; UNII: D7NLD2JX7U.

1 DEFINITION

Pirfenidone contains NLT 98.0% and NMT 102.0% of pirfenidone (C₁₂H₁₁NO), calculated on the dried basis.

2 IDENTIFICATION

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

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

[Note - Protect solutions containing pirfenidone from light.]

Solution A: 3.0 g/L of sodium phosphate monobasic anhydrous in water. Adjust with 0.1 N sodium hydroxide to a pH of 4.8 ± 0.2.

Solution B: Methanol

Solution C: Acetonitrile

Mobile phase: See Table 1.

Table 1

Standard solution: 1.3 mg/mL of USP Pirfenidone RS prepared as follows. Transfer a suitable amount of USP Pirfenidone RS to a suitable volumetric flask, and add 10% of the final volume of acetonitrile to dissolve. Dilute with Solution A to volume.

Sample solution: 1.3 mg/mL of Pirfenidone prepared as follows. Transfer a suitable amount of Pirfenidone to a suitable volumetric flask, and add 10% of the final volume of acetonitrile to dissolve. Dilute with Solution A to volume.

[Note - It is recommended not to exceed 1.45 mg/mL of USP Pirfenidone RS or Pirfenidone for the preparation of the Standard solution or the Sample solution, respectively.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 15-cm; 4-μm packing L1

Column temperature: 35°

Flow rate: 1.25 mL/min

Injection volume: 5 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of pirfenidone (C₁₂H₁₁NO) in the portion of Pirfenidone taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of pirfenidone from the Sample solution

r_S = peak response of pirfenidone from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

Organic Impurities

[Note - Protect solutions containing pirfenidone from light.]

Solution A, Solution B, Solution C, Mobile phase, and Chromatographic system: Proceed as directed in the Assay.

Diluent: Acetonitrile and Solution A (10:90)

System suitability stock solution: 0.15 mg/mL each of USP Pirfenidone Related Compound A RS and USP Pirfenidone Related Compound B RS in Diluent prepared as follows. Transfer a suitable amount of USP Pirfenidone Related Compound A RS and USP Pirfenidone Related Compound B RS to a suitable volumetric flask, and add 10% of the final volume of acetonitrile to dissolve. Dilute with Solution A to volume.

System suitability solution: 1.5 μg/mL each of USP Pirfenidone Related Compound A RS and USP Pirfenidone Related Compound B RS from the System suitability stock solution in Diluent

Standard stock solution: 1.3 mg/mL of USP Pirfenidone RS prepared as follows. Transfer a suitable amount of USP Pirfenidone RS to a suitable volumetric flask, and add 10% of the final volume of acetonitrile to dissolve. Dilute with Solution A to volume.

Standard solution: 1.6 μg/mL of USP Pirfenidone RS from the Standard stock solution in Diluent

Sample solution: 3.0 mg/mL of Pirfenidone in Diluent prepared as follows. Transfer a suitable amount of Pirfenidone to a suitable volumetric flask, and add 10% of the final volume of acetonitrile to dissolve. Dilute with Solution A to volume.

System suitability

Samples: System suitability solution and Standard solution

[Note - The relative retention times in Table 2 are provided as information that could aid in peak assignment.]

Table 2

^a 1,1'-(1,4-Phenylene)bis(5-methylpyridin-2(1H)-one).

Suitability requirements

Resolution: NLT 6.5 between pirfenidone related compound A and pirfenidone related compound B, System suitability solution

Relative standard deviation: NMT 10.0%, Standard solution

Signal-to-noise ratio: NLT 20, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Pirfenidone taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of pirfenidone from the Standard solution

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

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

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.03%.

Table 3

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry under vacuum (740 mbar) at 80° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Pirfenidone RS

USP Pirfenidone Related Compound A RS

5-Methylpyridin-2-amine.

C₆H₈N₂ 108.14

USP Pirfenidone Related Compound B RS

5-Methylpyridin-2(1H)-one.

C₆H₇NO 109.13