Diflunisal Tablets

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

Diflunisal Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of diflunisal (C₁₃H₈F₂O₃). 

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

2.1 Delete the following

2.1.1 B. THIN-LAYER CHROMATOGRAPHY

Standard solution: 10 mg/mL of USP Diflunisal RS in methanol and water (80:20)

Sample solution: Nominally 10 mg/mL of diflunisal prepared as follows. Transfer a quantity of finely ground Tablets, equivalent to about 100 mg of diflunisal, to a 10-mL volumetric flask. Add 2 mL of water, and sonicate for 5 min. Dilute with methanol to volume, sonicate for an additional 5 min, and pass through a suitable filter.

2.1.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 10 µL

Developing solvent system: n-Hexane, glacial acetic acid, and chloroform (17:3:2)

2.1.3 Analysis

Samples: Standard solution and Sample solution

Develop the chromatogram until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, air-dry, and examine under long-wavelength UV light.

Acceptance criteria: The R_F value of the principal spot of the Sample solution corresponds to that of the Standard solution. _{▲(USP 1-May-2020)}

2.2 Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. _{▲(USP 1-May-2020)}

3 ASSAY

Change to read:

3.1 PROCEDURE

Mobile phase: Methanol, acetonitrile, glacial acetic acid, and water (40:17:6:45)

Diluent: Acetonitrile and water (60:40)

Standard solution: 0.1 mg/mL of USP Diflunisal RS in Diluent. Sonicate to dissolve as needed.

Sample stock solution: Nominally 1 mg/mL of diflunisal prepared as follows. Finely powder Tablets (NLT 20). Transfer a quantity of the powder, equivalent to about 100 mg of diflunisal, to a 100-mL volumetric flask. Add 5 mL of water and sonicate for 5 min. Add 60 mL of acetonitrile, and sonicate with occasional shaking for 10 min. Dilute with water to volume. Pass through a suitable filter of 0.45-µm pore size. Discard the first few milliliters of the filtrate.

Sample solution: Nominally 0.1 mg/mL of diflunisal in Diluent from Sample stock solution

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability..)

Mode: LC

Detector: UV 254 nm. For Identification B, use a diode array detector in the range of 200-400 nm.

Column: 4.6-mm x 15-cm; 5-µm packing 11

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of diflunisal _{▲(USP 1-May-2020)}

3.1.2 System suitability

Sample: Standard solution

3.1.3 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of diflunisal (C₁₃H₈F₂O₃) in the portion of Tablets taken: 2

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

r_U = peak response of diflunisal from the Sample solution

r_S = peak response of diflunisal from the Standard solution 

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

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 Change to read

4.1.1 DISSOLUTION (711).

Citric acid solution: Dissolve 7 g of anhydrous citric acid in 100 mL of water.

0.1 M tris buffer: Dissolve 121 g of tris(hydroxymethyl)aminomethane (THAM) in 9 L of water. Adjust with Citric acid solution to a pH of 7.45, at 25°. Dilute with water to 10.0 L, equilibrate to 37°, and adjust to a pH of 7.20, if necessary.

Medium: 0.1 M tris buffer, 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: A known concentration of USP Diflunisal RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary.

4.1.2 Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).) _{▲(USP 1-May-2020)}

Mode: UV

Analytical wavelength: 306 nm

4.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of diflunisal (C₁₃H₈F₂O₃) dissolved:

                Result = (A_U/A_S) x C_S x D x V x (1/L) x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

D = dilution factor of the Sample solution

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

(USP 1-May-2020)

Tolerances: NLT 80% (Q) of the labeled amount of diflunisal (C₁₃H₈F₂O₃) is dissolved.

4.2 Change to read

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

(USP 1-May-2020)

5 IMPURITIES

5.1 Add the following

5.1.1 ORGANIC IMPURITIES

Mobile phase: Methanol, acetonitrile, glacial acetic acid, and water (36:15:6:50)

Diluent: Acetonitrile and water (60:40)

Sensitivity solution: 1 µg/mL of USP Diflunisal RS in Diluent. Sonicate to dissolve as needed.

Standard solution: 2 µg/mL of USP Diflunisal RS in Diluent. Sonicate to dissolve as needed.

Sample solution: Prepare as directed in the Sample stock solution in the Assay.

5.1.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 10 µL

5.1.3 System suitability

Samples: Sensitivity solution and Standard solution

5.1.4 Suitability requirements

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 10.0%, Standard solution

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

5.1.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any unspecified degradation product in the portion of Tablets taken:

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

r_U = peak response of any unspecified degradation product from the Sample solution

r_S = peak response of diflunisal from the Standard solution s

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

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

Acceptance criteria: See Table 1.

Table 1

^a Process impurity for identification only. It is not to be reported or included in the total degradation products.

^b 2',4'-Difluorobiphenyl-4-ol.

^c 1-(2',4'-Difluorobiphenyl-4-yl)ethan-1-one.

^d 2',4'-Difluorobiphenyl-4-yl acetate.

^e 2,4-Difluorobiphenyl.

(USP 1-May-2020)

6 ADDITIONAL REQUIREMENTS

6.1 Change to read

PACKAGING AND STORAGE: Preserve in well-closed containers. Store at controlled room temperature. _{▲(USP 1-May-2020)}

USP REFERENCE STANDARDS (11)

USP Diflunisal RS