Sulindac

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

Sulindac contains NLT 98.0% and NMT 102.0% of sulindac (C₂₀H₁₇FO₃S), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy : 197M (CN 1-M  -2020)

Change to read:

B. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Ultraviolet-Visible Spectroscopy : 197U (CN 1-MAY-2020)

Analytical wavelength: 284 nm

Medium: Hydrochloric acid in methanol (1 in 120) Sample solution: 15 µg/mL in Medium

Acceptance criteria: Absorptivities, calculated on the dried basis, do not differ by more than 3.0%.

C. 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

Solution A: 0.1% Formic acid in water Solution B: 0.1% Formic acid in acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (50:50)

System suitability solution: 0.003 mg/mL each of USP Sulindac RS, USP Sulindac Related Compound A RS, USP Sulindac Related Compound B RS, and USP Sulindac Related Compound C RS in Diluent

Standard solution: 0.2 mg/mL of USP Sulindac RS in Diluent

Sample solution: 0.2 mg/mL of Sulindac in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: 330 nm

Column: 2.1-mm × 15-cm; 1.7-µm packing L1

Column temperature: 45°

Flow rate: 0.3 mL/min

Injection volume: 2 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE—The relative retention times for sulindac related compound A, sulindac related compound B, and sulindac related compound C are 1.25, 1.34, and 1.67, respectively.]

Suitability requirements

Resolution: NLT 4.0 between sulindac and sulindac related compound A and between sulindac related compound A and sulindac related compound B, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of sulindac (C₂₀H₁₇FO₃S) in the portion of Sulindac taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

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

4 IMPURITIES

RESIDUE ON IGNITION 〈281〉: NMT 0.1%

RESIDUAL SOLVENTS 〈467〉

Solvent: Dimethylsulfoxide

Acceptance criteria: Meets the requirements except that chloroform is NMT 500 ppm

ORGANIC IMPURITIES

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

Standard solution: 0.6 µg/mL of USP Sulindac RS and 3 µg/mL each of USP Sulindac Related Compound A RS, USP Sulindac Related Compound B RS, and USP Sulindac Related Compound C RS in Diluent. Sonicate for 2–5 min.

Sample solution: 600 µg/mL of Sulindac in Diluent. Sonicate for 2–5 min. System suitability

Sample: Standard solution Suitability requirements

Resolution: NLT 4.0 between sulindac and sulindac related compound A and between sulindac related compound A and sulindac related compound B

Relative standard deviation: NMT 2.0% for any peak Analysis

Samples: Standard solution and Sample solution

Calculate the percentages of sulindac related compound A, sulindac related compound B, and sulindac related compound C in the portion of Sulindac taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of the specified impurity from the Sample solution

r_S = peak response of the corresponding related compound from the Standard solution

C_S = concentration of the corresponding related compound in the Standard solution (µg/mL)

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

Calculate the percentage of any individual unspecified impurity in the portion of Sulindac taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any individual unspecified impurity from the Sample solution

r_S = peak response of sulindac from the Standard solution

C_S = concentration of USP Sulindac RS in the Standard solution (µg/mL)

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

Acceptance criteria: See Table 2.

Table 2

^a (E)-2-{5-Fluoro-2-methyl-1-[4-(methylsulfinyl)benzylidene]-1H-inden-3-yl}acetic acid.

^b (Z)-2-{5-Fluoro-2-methyl-1-[4-(methylsulfonyl)benzylidene]-1H-inden-3-yl}acetic acid.

^c (Z)-2-{5-Fluoro-2-methyl-1-[4-(methylthio)benzylidene]-1H-inden-3-yl}acetic acid.

5 SPECIFIC TESTS

LOSS ON DRYING 〈731〉

Analysis: Dry under vacuum at 100° for 2 h. Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

USP REFERENCE STANDARDS 〈11〉

USP Sulindac RS

USP Sulindac Related Compound A RS

(E)-2-{5-Fluoro-2-methyl-1-[4-(methylsulfinyl)benzylidene]-1H-inden-3-yl}acetic acid. C₂₀H₁₇FO₃S    356.41

USP Sulindac Related Compound B RS

(Z)-2-{5-Fluoro-2-methyl-1-[4-(methylsulfonyl)benzylidene]-1H-inden-3-yl}acetic acid. C₂₀H₁₇FO₄S    372.41

USP Sulindac Related Compound C RS

(Z)-2-{5-Fluoro-2-methyl-1-[4-(methylthio)benzylidene]-1H-inden-3-yl}acetic acid. C₂₀H₁₇FO₂S    340.41