Gemfibrozil

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

C₁₅H₂₂O₃ 250.33

Pentanoic acid, 5-(2,5-dimethylphenoxy)-2,2-dimethyl-;

2,2-Dimethyl-5-(2,5-xylyloxy)valeric acid CAS RN^®: 25812-30-0; UNII: Q8X02027X3.

1 DEFINITION

Gemfibrozil contains NLT 98.0% and NMT 102.0% of gemfibrozil (C₁₅H₂₂O₃), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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

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

Mobile phase: Add 10 mL of glacial acetic acid to 800 mL of methanol in a 1000-mL volumetric flask, dilute with water to volume, and pass through a membrane filter.

System suitability solution: 0.2 mg/mL of gemfibrozil and 0.05 mg/mL of 2,5-dimethylphenol in Mobile phase

Standard stock solution: 1 mg/mL of USP Gemfibrozil RS in methanol

Standard solution: 0.2 mg/mL of USP Gemfibrozil RS in Mobile phase from the Standard stock solution

Sample stock solution: 1 mg/mL of Gemfibrozil in methanol

Sample solution: 0.2 mg/mL of Gemfibrozil in Mobile phase from the Sample stock solution

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 276 nm

Column: 3.9-mm x 30-cm; packing L1

Flow rate: 0.8 mL/min

Injection volume: 10 µL

3.3 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

[NOTE-The elution order is 2,5-dimethylphenol, followed by gemfibrozil.]

Resolution: NLT 8.0 between gemfibrozil and 2,5-dimethylphenol, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of gemfibrozil (C₁₅H₂₂O₃) in the portion of Gemfibrozil 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

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

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

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

4 IMPURITIES

ORGANIC IMPURITIES

Mobile phase: Add 10 mL of glacial acetic acid to 750 mL of methanol in a 1000-mL volumetric flask, dilute with water to volume, and pass through a membrane filter.

Peak identification solution: 0.2 mg/mL of USP Gemfibrozil RS, 0.05 mg/mL of USP Gemfibrozil Related Compound A RS, and 0.05 mg/mL of 2,5-dimethylphenol in Mobile phase

Standard stock solution: 0.1 mg/mL each of USP Gemfibrozil RS and USP Gemfibrozil Related Compound A RS in methanol

Standard solution: 0.01 mg/mL each of USP Gemfibrozil RS and USP Gemfibrozil Related Compound A RS in Mobile phase from the Standard stock solution

Sample solution: 10 mg/mL of Gemfibrozil in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 276 nm

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

Flow rate: 1 mL/min

Injection volume: 100 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 3.0% for each peak

Analysis

Chromatograph the Peak identification solution, and identify the components on the basis of their relative retention times. The relative retention times for 2,5-dimethylphenol, gemfibrozil, and gemfibrozil related compound A are 0.35, 1.0, and 2.1, respectively.

Samples: Standard solution and Sample solution

Calculate the percentage of gemfibrozil related compound A in the portion of Gemfibrozil taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak area of gemfibrozil related compound A from the Sample solution

r_S = peak area of gemfibrozil related compound A from the Standard solution

C_S = concentration of USP Gemfibrozil Related Compound A RS in the Standard solution (mg/mL)

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

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

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak area of each individual impurity from the Sample solution

r_S = peak area for gemfibrozil from the Standard solution

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

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

Acceptance criteria

Gemfibrozil related compound A: NMT 0.1%

Any other impurity: NMT 0.1%

Total impurities: NMT 0.5%

5 SPECIFIC TESTS

WATER DETERMINATION, Method (921): NMT 0.25%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers.

6.2 USP REFERENCE STANDARDS (11)

USP Gemfibrozil RS

USP Gemfibrozil Related Compound A RS

(E,Z)-2,2-Dimethyl-5-[2,5-dimethyl-4-(propene-1-yl)phenoxy]valeric acid.

C₁₈H₂₆O₃ 290.40