Fenofibrate

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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C₂₀H₂₁CIO₄ 360.83

Isopropyl 2-[p-(p-chlorobenzoyl)phenoxy]-2-methylpropanoate CAS RN^®: 49562-28-9; UNII: U202363UOS.

1 DEFINITION

Fenofibrate contains NLT 98.0% and NMT 102.0% of C₂₀H₂₁CIO₄, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

3 ASSAY

3.1 PROCEDURE

Mobile phase: Acetonitrile and water acidified with phosphoric acid to a pH of 2.5 (7:3)

Standard solution: 1 mg/mL of USP Fenofibrate RS in Mobile phase

Sample solution: 1 mg/mL of Fenofibrate in Mobile phase

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 286 nm

Column: 4.0-mm x 25-cm; packing L1

Flow rate: 1.0 mL/min

Injection size: 5 µL

3.3 System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 1.0% for six replicate injections

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₂₀H₂₁CIO₄ in the portion of Fenofibrate taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution s

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

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

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

4 IMPURITIES

4.1 INORGANIC IMPURITIES

4.1.1 RESIDUE ON IGNITION (281)

NMT 0.1%, determined on 1.0 g

4.1.2 CHLORIDE AND SULFATE, Chloride (221)

Sample solution: Add 25 mL of water to 5.0 g of Fenofibrate, and heat at 50° for 10 min. Cool, dilute with water to 50.0 mL, filter, and use the filtrate. [NOTE-Retain the remaining portion of the Sample solution for the test for Chloride and Sulfate, Sulfate.]

Analysis: Use 10 mL of the Sample solution.

Acceptance criteria: It shows no more chloride than corresponds to 0.15 mL of 0.020 N hydrochloric acid (0.01%).

4.1.3 CHLORIDE AND SULFATE, Sulfate (221)

Sample: Use the Sample solution prepared in the test for Chloride and Sulfate, Chloride.

Analysis: Use 10 mL of the Sample.

Acceptance criteria: It shows no more sulfate than corresponds to 0.15 mL of 0.020 N sulfuric acid (0.01%).

4.2 ORGANIC IMPURITIES

4.2.1 PROCEDURE

Mobile phase: Acetonitrile and water acidified with phosphoric acid to a pH of 2.5 (7:3)

Impurity standard solution: 1 µg/mL each of USP Fenofibrate RS, USP Fenofibrate Related Compound A RS, and USP Fenofibrate Related Compound B RS, and 2 µg/mL of USP Fenofibrate Related Compound C RS in Mobile phase

Sample solution: 1 mg/mL of Fenofibrate in Mobile phase

4.2.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 286 nm

Column: 4.0-mm x 25-cm; packing L1

Flow rate: 1.0 mL/min

Injection size: 20 μL

4.2.3 System suitability

Sample: Impurity standard solution

Suitability requirements

Resolution: NLT 1.5 between fenofibrate related compound A and fenofibrate related compound B

4.2.4 Analysis

Samples: Impurity standard solution and Sample solution

Identify the fenofibrate peak and the peaks due to the impurities and degradation products listed in Impurity Table 1.

Measure the responses for the major peaks, and calculate the percentage of each of fenofibrate related compound A, fenofibrate related compound B, and fenofibrate related compound C in the portion of Fenofibrate taken:

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

r_U = peak response of appropriate fenofibrate related compound from the Sample solution

r_S = peak response of appropriate fenofibrate related compound from the Impurity standard solution

C_S = concentration of the appropriate fenofibrate related compound in the Impurity standard solution (µg/mL)

C_U = concentration of Fenofibrate in the Sample solution (µg/mL)

Calculate the percentage of any other impurity in the portion of Fenofibrate taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of fenofibrate from the Impurity standard solution

C_S = concentration of fenofibrate in the Impurity standard solution (µg/mL)

C_U = concentration of Fenofibrate in the Sample solution (µg/mL)

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 0.5%

Impurity Table 1

^a Fenofibrate related compound A.

^b Fenofibrate related compound B.

^c Fenofibrate related compound C.

5 SPECIFIC TESTS

5.1 MELTING RANGE OR TEMPERATURE, Class la(741)

79°-82°

5.2 ACIDITY

Sample: 1.0 g

Analysis: Dissolve the Sample in 50 mL of alcohol previously neutralized to phenolphthalein TS, and titrate with 0.1 N sodium hydroxide VS.

Acceptance criteria: NMT 0.2 mL is required to change the color of the indicator to pink.

5.3 LOSS ON DRYING (731)

Analysis: Dry a sample in a vacuum over phosphorus pentoxide at 60° to constant weight.

Acceptance criteria: NMT 0.5%

5.4 COLOR AND ACHROMICITY (631)

Reference solution: Mix 5 mL of Matching Fluid G and 95 mL of dilute hydrochloric acid (1 in 40).

Sample solution: 50 mg/mL of Fenofibrate in acetone

Analysis: Proceed as directed in the chapter.

Acceptance criteria: The Sample solution is not more intensely colored than the Reference solution.

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed, light-resistant containers. Store at room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Fenofibrate RS

USP Fenofibrate Related Compound A RS

(4-Chlorophenyl)(4-hydroxyphenyl)methanone.

USP Fenofibrate Related Compound B RS

2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropanoic acid, or fenofibric acid.

USP Fenofibrate Related Compound C RS

1-Methylethyl 2-[[2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoyl]oxy]-2-methylpropanoate.