Etodolac

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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Pyrano[3,4-b]indole-1-acetic acid, 1,8-diethyl-1,3,4,9-tetrahydro-(±)-;

1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-ylacetic acid CAS RN^®: 41340-25-4; UNII: 2M36281008.

1 DEFINITION

Etodolac contains NLT 98.0% and NMT 102.0% of etodolac(C₁₇H₂₁NO₃), calculated on the anhydrous basis.

2 IDENTIFICATION

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 A. Spectroscopic Identification Tests (197), Infrared Spectroscopy: 197A or 197K

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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

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Procedure

Protect solutions containing etodolac from light.

Solution A: 0.77 g/L of ammonium acetate in water

Solution B: Acetonitrile and Solution A (90:10)

Mobile phase: See Table 1. Return to the original conditions to re-equilibrate the system. [Note—A re-equilibration time of 5 min may be used.]

Standard solution: 0.2 mg/mL of USP Etodolac RS in acetonitrile

Sample solution: 0.2 mg/mL of Etodolac in acetonitrile

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 15-cm; 3.5-μm packing L26

Temperatures

Autosampler: 5°

Column: 35°

Flow rate: 1 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 etodolac (C₁₇H₂₁NO₃) in the portion of Etodolac taken:

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

r_U = peak response of etodolac from the Sample solution

r_S = peak response of etodolac the Standard solution

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

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

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

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

LIMIT OF CHLORIDE

Sample: 1.0 g of Etodolac

Titrimetric system

(See Titrimetry (541).)

Mode: Direct titration

Titrant: 0.01 N silver nitrate

Endpoint detection: Potentiometric

Analysis: Dissolve the Sample in 60 ml. of methanol, dilute with 10 ml of water and add 20 ml, of 2 N nitric acid. Titrate with the Titrant.

Acceptance criteria: NMT 300 ppm

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LIMIT OF ALCOHOL AND METHANOL

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ORGANIC IMPURITIES

Protect solutions containing etodolac from light.

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

Mobile phase: See Table 2. Return to the original conditions and re-equilibrate the system. [Note-A re-equilibration time of 15 min may be used]

System suitability solution: 1.0 mg/mL of USP Etodolac Peak Identi

cation Mixture RS in acetonitrile. Sonicate to dissolve as needed.

Standard solution: 0.002 mg/mL of USP Etodolac RS in acetonitrile. Sonicate to dissolve as needed.

Sensitivity solution: 0.5 μg/mL of USP Etodolac RS in acetonitrile from the Standard solution

Sample solution: 1.0 mg/mL of Etodolac in acetonitrile. Sonicate to dissolve as needed.

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT 3.0 between etodolac and 7-ethyltrypthanol (etodolac related compound H), System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of etodolac from the Standard solution

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

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

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.05%

^a 1-Ethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-ylacetic acid.

^b 1-Ethyl-8-methyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-ylacetic acid.

^c 8-Ethyl-1-methyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-ylacetic acid.

^d 2-(7-Ethyl-1H-indol-3-yl)ethan-1-ol.

^e 1-Ethyl-8-isopropyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-ylacetic acid.

^f 8-Ethyl-1-propyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-ylacetic acid.

^g 1-Ethyl-8-propyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-ylacetic acid.

^h 8-Ethyl-1-isopropyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-ylacetic acid.

ⁱ 3-(7-Ethyl-1H-indol-3-yl)-3-[7-ethyl-3-(2-hydroxyethyl)-1H-indol-2-yl]pentanoic acid.

^j Methyl 2-(1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetate.

5 SPECIFIC TESTS

Water Determination (921), Method I: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

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