Diclofenac Sodium and Misoprostol Delayed-Release 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 

Diclofenac Sodium and Misoprostol Delayed-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) and NLT 90.0% and NMT 110.0% of the labeled amount of misoprostol (C₂₂H₃₈O₅). 

2 IDENTIFICATION 

2.1 A. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U 

Misoprostol 

Diluent: Methanol and water (4:1) 

Standard solution: 16 µg/mL of USP Misoprostol RS in Diluent. [Note—If outer misoprostol layers of the Tablets contain hypromellose, the Standard solution should also contain hypromellose at the same concentration as in the Sample solution.] 

Sample solution: Gently break up one by one a quantity of Tablets equivalent to 0.4 mg of misoprostol, and remove the inner diclofenac layers. [Note—Keep the diclofenac layers for Identication A, Diclofenac sodium.] Transfer the outer misoprostol layers to a 25-mL volumetric ask. Add about 15 mL of Diluent, shake for 30 min, dilute with Diluent to volume, and mix well. Transfer a portion of the solution into a glass centrifuge tube, and centrifuge for 10 min under refrigerated conditions (10°). Use the supernatant.

Blank: Diluent 

Cell: 1 cm 

Acceptance criteria: Meet the requirements 

Diclofenac sodium 

Standard solution: 0.1 mg/mL of USP Diclofenac Sodium RS in methanol 

Sample solution: Transfer the diclofenac inner layers reserved from Identication A, Misoprostol, to a 100-mL volumetric ask. Add about 60 mL of methanol, shake for 10 min, dilute with methanol to volume, and mix well. Further dilute a suitable volume of the solution to obtain a solution containing about 0.1 mg/mL of diclofenac sodium, based on the label claim. Pass a portion of the solution through a polytetrauoroethylene (PTFE) with glass microber (GMF) lter of 0.45-µm pore size.1 Discard the rst few milliliters of the ltrate, and use the ltrate. 

Blank: Methanol 

Cell: 0.05 cm 

Acceptance criteria: Meet the requirements 

2.2 B. 

Misoprostol: The retention time of the misoprostol peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay for Misoprostol. 

Diclofenac sodium: The retention time of the diclofenac peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay for Diclofenac Sodium. 

3 ASSAY 

3.1 Misoprostol 

Buffer: Prepare 0.025 M monobasic potassium phosphate, pH 6.5, as follows. Adjust a solution containing 3.4 g/L of monobasic potassium phosphate in water with 1 N sodium hydroxide to a pH of 6.5. 

Mobile phase: Acetonitrile and Buffer (45:55) 

Standard solution: 0.01 mg/mL of USP Misoprostol RS in Mobile phase, using sonication as needed 

Sample solution: Nominally 0.01 mg/mL of misoprostol prepared as follows. Using a quantity of Tablets equivalent to 5 mg of misoprostol, place 1 Tablet at a time on its edge inside a well-folded piece of weighing paper. Tap very carefully the edge of the Tablet with a pestle to separate the Tablet into the outer and inner layers. Remove the inner core containing diclofenac sodium. Transfer the outer portions of the Tablets, containing misoprostol, into a 500-mL volumetric ask containing a magnetic stir bar, and add 250 mL of acetonitrile. Stir the ask for 1 h. Add 150 mL of water, and stir for an additional 30 min or until the Tablets are completely disintegrated. Remove the stir bar, rinse it inside the ask with water, dilute with water to volume, and mix well. Transfer a portion of the solution into a glass centrifuge tube, and centrifuge for 10 min under refrigerated conditions (10°). Use the supernatant. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 200 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L10 

Temperatures 

Autosampler: 10° 

Column: 35° 

Flow rate: 1.0 mL/min 

Injection volume: 80 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of misoprostol (C₂₂H₃₈O₅) in the portion of Tablets 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 Misoprostol RS in the Standard solution (mg/mL) 

C_u = nominal concentration of misoprostol in the Sample solution (mg/mL) 

Acceptance criteria: 90.0%–110.0% 

3.2 Diclofenac Sodium 

Buffer: Mix equal volumes of 0.01 M phosphoric acid and 0.01 M monobasic sodium phosphate. If necessary, adjust with additional portions of the appropriate component to a pH of 2.5. 

Mobile phase: Methanol and Buffer (70:30) 

Diluent: Methanol and water (70:30) 

System suitability solution: 20 µg/mL of diethyl phthalate, 8 µg/mL of USP Diclofenac Related Compound A RS, and 0.75 mg/mL of USP Diclofenac Sodium RS in Diluent 

Standard solution: 0.75 mg/mL of USP Diclofenac Sodium RS in Diluent, using sonication as needed 

Sample stock solution: Transfer a quantity of Tablets, equivalent to 1500 mg of diclofenac sodium, into a 1000-mL volumetric ask containing a magnetic stir bar. Add 700 mL of Diluent, and stir for 60 min or until the Tablets are completely disintegrated. Remove the stir bar, rinse it with Diluent, and sonicate the sample for 15 min. Allow the sample to cool to room temperature, dilute with Diluent to volume, and mix well. 

Sample solution: Nominally 0.75 mg/mL of diclofenac sodium prepared as follows. Transfer 10.0 mL of the Sample stock solution into a 20- mL volumetric ask, and dilute with Diluent to volume. Pass a portion of the solution through a PTFE with GMF lter of 0.45-µm pore size, discarding the rst few milliliters of the ltrate. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L7 

Flow rate: 1.0 mL/min 

Injection volume: 10 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times for diethyl phthalate, diclofenac related compound A, and diclofenac are about 0.6, 0.7, and 1.0, respectively.] 

Suitability requirements 

Resolution: NLT 2.2 between the diethyl phthalate and diclofenac related compound A peaks; NLT 6.5 between the diclofenac related compound A and diclofenac peaks, System suitability solution 

Tailing factor: NMT 2, Standard solution 

Relative standard deviation: NMT 2.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) in the portion of Tablets 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 Diclofenac Sodium RS in the Standard solution (mg/mL) 

C_u = nominal concentration of diclofenac sodium in the Sample solution (mg/mL) 

Acceptance criteria: 90.0%–110.0% 

4 PERFORMANCE TESTS 

Change to read: 

4.1 Dissolution 〈711〉 

Test 1 

Misoprostol 

Medium: water; 500 mL, deaerated 

Apparatus 2: 50 rpm 

Time: 20 min 

Buffer: Prepare as directed in the Assay for Misoprostol. 

Mobile phase: Acetonitrile and Buffer (42:58) 

Standard stock solution: Transfer 4 mg of USP Misoprostol RS into a 100-mL volumetric ask, add 20 mL of acetonitrile, and shake for about 15 min. If the outer misoprostol layers of the Tablets contain hypromellose, add a suitable amount of hypromellose to the ask to achieve the same nal concentration of hypromellose in the Standard solution as expected in the Sample solution. Add 20 mL of water, and sonicate for about 2 min. Add water up to the neck of the ask, and allow the solution to cool to room temperature before the nal dilution to volume. 

Standard solution: About 0.0004 mg/mL of USP Misoprostol RS prepared as follows. Dilute 2.0 mL of the Standard stock solution with Medium to 200 mL. 

Sample solution: Pass a portion of the solution under test through a suitable lter of 10-µm pore size. 

Chromatographic system: Proceed as directed in the Assay for Misoprostol, except for Injection volume. 

Injection volume: 200 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2 

Relative standard deviation: NMT 5.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of misoprostol (C₂₂H₃₈O₅) dissolved:  

Result = (r_u/r_s) × (C_s/L) × V × 100 

r_u = peak response from the Sample solution 

r_s = peak response from the Standard solution 

C_s = concentration of USP Misoprostol RS in the Standard solution (mg/mL) 

L = label claim for misoprostol (mg/Tablet) 

V = volume of Medium, 500 mL 

Tolerances: NLT 75% (Q) of the labeled amount of misoprostol (C₂₂H₃₈O₅) is dissolved. 

Diclofenac sodium 

Proceed as directed in Dissolution 〈711〉, Procedure, Apparatus 1 and Apparatus 2, Delayed-Release Dosage Forms, Method A Procedure. Acid stage medium: 0.1 N hydrochloric acid; 750 mL, deaerated 

Buffer stage medium: After 2 h, add 250 mL of 0.2 M tribasic sodium phosphate to the Acid stage medium and, if needed, adjust with either 2 N hydrochloric acid or 2 N sodium hydroxide to a pH of 6.8. 

Apparatus 2: 100 rpm 

Times: 2 h for Acid stage; 45 min for Buffer stage 

Buffer: 0.025 M monobasic potassium phosphate buffer with a pH of 3.0 prepared as follows. Adjust a solution containing 3.4 g/L of monobasic potassium phosphate in water with phosphoric acid to a pH of 3.0. 

Mobile phase: Acetonitrile and Buffer (60:40) 

Standard stock solution: 0.68 mg/mL of USP Diclofenac Sodium RS, rst dissolved in 0.1 N sodium hydroxide using about 10% of the nal volume, and then diluted with water to volume 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 276 nm 

Column: 4.6-mm × 15-cm; 5-µm packing L7 

Flow rate: 1.0 mL/min 

Injection volume: 10 µL 

Acid stage 

Acid stage standard solution: 13.6 µg/mL of USP Diclofenac Sodium RS prepared as follows. Transfer 2.0 mL of the Standard stock solution to a 100-mL volumetric ask, and dilute with a mixture of 0.1 N hydrochloric acid and 5 N sodium hydroxide (900:20) to volume. Acid stage sample solution: Run the test in Acid stage medium for 2 h. Withdraw a 10-mL aliquot, transfer it to a ask containing 1.0 mL of 1 N sodium hydroxide, and mix well. Pass a portion of this solution through a suitable lter of 10-µm pore size. 

System suitability 

Sample: Acid stage standard solution 

Suitability requirements 

Tailing factor: NMT 2 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Acid stage standard solution and Acid stage sample solution 

Calculate the percentage of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) dissolved during the Acid stage: 

Result = (r_u/r_s) × (C_s/L) × V × D × 100 

r_u = peak response from the Acid stage sample solution 

r_s = peak response from the Acid stage standard solution 

C_s = concentration of USP Diclofenac Sodium RS in the Acid stage standard solution (mg/mL) 

L = label claim for diclofenac sodium (mg/Tablet) 

V = volume of Acid stage medium, 750 mL 

D = dilution factor for the Acid stage sample solution, 1.1 

Tolerances: NMT 10% of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) is dissolved. The percentage of the labeled amount of diclofenac sodium dissolved at the time specied conforms to Dissolution 〈711〉, Acceptance Table 3. 

Buffer stage 

Buffer stage standard solution: 13.6 µg/mL of USP Diclofenac Sodium RS prepared as follows. Transfer 2.0 mL of the Standard stock solution to a 100-mL volumetric ask, and dilute with Buffer stage medium to volume. 

Buffer stage sample solution: Pass a portion of the solution under test through a suitable lter of 10-µm pore size. System suitability 

Sample: Buffer stage standard solution 

Suitability requirements 

Tailing factor: NMT 2 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Acid stage sample solution, Buffer stage standard solution, and Buffer stage sample solution 

Calculate the percentage of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) dissolved during the Buffer stage: 

Result = (r_u/r_s) × (C_s/L) × (V − V_s) × 100 

r_u = peak response from the Buffer stage sample solution 

r_s = peak response from the Buffer stage standard solution 

C_s = concentration of USP Diclofenac Sodium RS in the Buffer stage standard solution (mg/mL) 

L = label claim for diclofenac sodium (mg/Tablet) 

V = volume of Buffer stage medium, 1000 mL 

V_s = volume of the Acid stage sample solution, 10 mL 

Tolerances: NLT 75% (Q) of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) is dissolved. The percentage of the labeled amount of diclofenac sodium dissolved at the time specied conforms to Dissolution 〈711〉, Acceptance Table 4. 

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. 

Misoprostol 

Medium: Water; 500 mL 

Apparatus 2: 50 rpm 

Time: 15 min 

Solution A: 24.5 g/L of phosphoric acid in water 

Mobile phase: Acetonitrile, water, and Solution A (50:50:0.5) 

Diluent: Acetonitrile and water (60:40) 

Standard stock solution: 0.01 mg/mL of USP Misoprostol RS prepared as follows. Transfer 10 mg of USP Misoprostol RS into a 100-mL volumetric ask, add 10 mL of acetonitrile, and swirl the ask to disperse. If the outer misoprostol layers of the Tablets contain hypromellose, add a suitable amount of hypromellose to the ask to achieve the same nal concentration of hypromellose in the Standard solution as expected in the Sample solution. Add about 60 mL of Diluent and sonicate to dissolve. Dilute with Diluent to volume. Further dilute 5.0 mL of this solution with Diluent to 50 mL. 

Standard solution: 0.0004 mg/mL of USP Misoprostol RS in Medium from the Standard stock solution 

Sample solution: Pass a portion of the solution under test through a PVDF lter of 0.45-μm pore size, discarding the rst 5 mL of the ltrate. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 200 nm 

Column: 4.6-mm × 25-cm; 5-μm packingL11 

Autosampler temperature: 5° 

Flow rate: 1 mL/min 

Injection volume: 100 µL System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 5.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of misoprostol (C₂₂H₃₈O₅) dissolved: 

Result = (r_u/r_s) × C_s × V × (1/L) × 100 

r_u = peak response of misoprostol from the Sample solution 

r_s = peak response of misoprostol from the Standard solution 

C_s = concentration of USP Misoprostol RS in the Standard solution (mg/mL)  

V = volume of Medium, 500 mL 

L = label claim for misoprostol (mg/Tablet) 

Tolerances: NLT 80% (Q) of the labeled amount of misoprostol (C₂₂H₃₈O₅) is dissolved. 

Diclofenac sodium 

Acid stage medium: 0.1 N hydrochloric acid; 750 mL 

Buffer: 76.02 g/L of tribasic sodium phosphate dodecahydrate in water 

Buffer stage medium: 0.1 N hydrochloric acid and Buffer (75:25). Adjust with either 2 N hydrochloric acid or 2 N sodium hydroxide to a pH of 6.8 ± 0.1; 1000 mL. 

Apparatus 2: 100 rpm 

Times 

Acid stage: 2 h 

Buffer stage: 60 min 

Diluent: Methanol and water (50:50) 

Acid stage 

Acid stage standard stock solution: 0.75 mg/mL of USP Diclofenac Sodium RS in Diluent 

Acid stage standard solution: (L/10,000) mg/mL of USP Diclofenac Sodium RS in Buffer stage medium, where L is the label claim of diclofenac sodium in milligrams per Tablet 

Acid stage sample solution: Run the test in Acid stage medium for 2 h. Withdraw 13.0 mL of the solution under test and dilute 7.5 mL of this solution with Buffer to 10.0 mL. Pass a portion of this solution through a PVDF lter of 0.45-μm pore size, discarding the rst 5 mL. Replace the aliquot withdrawn for analysis with 13.0 mL of fresh Acid stage medium. 

Instrumental conditions 

(See Ultraviolet-Visible Spectroscopy 〈857〉.) 

Mode: UV 

Analytical wavelength: 276 nm 

Cell: 1 cm 

Blank: Buffer stage medium 

Analysis 

Samples: Acid stage standard solution and Acid stage sample solution 

Calculate the percentage of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) dissolved during the Acid stage:  

Result = (A_u/A_s) × C_s × V × D × (1/ L) × 100 

A_u = absorbance of the Sample solution 

A_s = absorbance of the Standard solution 

C_s = concentration of USP Diclofenac Sodium RS in the Acid stage standard solution (mg/mL) 

V = volume of Acid stage medium, 750 mL 

D = dilution factor for the Acid stage sample solution, 1.33 

L = label claim for diclofenac sodium (mg/Tablet) 

Tolerances: NMT 10% of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) is dissolved. The percentage of the labeled amount of diclofenac sodium dissolved at the time specied conforms to Dissolution 〈711〉, Acceptance Table 3. 

Buffer stage 

Buffer stage standard stock solution: 0.5 mg/mL of USP Diclofenac Sodium RS in Diluent 

Buffer stage standard solution: 0.02 mg/mL of USP Diclofenac Sodium RS in Buffer stage medium from the Buffer stage standard stock solution 

Buffer stage sample solution: After 2 h of Acid stage dissolution, add 250 mL of Buffer to each vessel containing the remaining Tablets. Adjust, if necessary, with either 2 N hydrochloric acid or 2 N sodium hydroxide to a pH of 6.8 ± 0.1. After 60 min pass a portion of the solution under test through a PVDF lter of 0.45-μm pore size, discarding the rst 5 mL. Make dilutions with Buffer stage medium as necessary to obtain a solution of 0.02 mg/mL of diclofenac sodium. 

Instrumental conditions 

(See Ultraviolet-Visible Spectroscopy 〈857〉.) 

Mode: UV 

Analytical wavelength: 276 nm 

Cell: 1 cm 

Blank: Buffer stage medium 

Analysis 

Samples: Buffer stage standard solution and Buffer stage sample solution 

Calculate the percentage of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) dissolved during the Buffer stage: 

Result = (A_u/A_s) × C_s × V × D × (1/ L) × 100 

A_u = absorbance of the Sample solution 

A_s = absorbance of the Standard solution 

C_s = concentration of USP Diclofenac Sodium RS in the Buffer stage standard solution (mg/mL)  

V = total volume of Buffer stage medium, 1000 mL 

D = dilution factor for the Buffer stage sample solution 

L = label claim for diclofenac sodium (mg/Tablet) 

Tolerances: NLT 80% (Q) of the labeled amount of diclofenac sodium (C₁₄H₁₀Cl₂NNaO₂) is dissolved. The percentage of the labeled amount of diclofenac sodium dissolved at the time specied conforms to Dissolution 〈711〉, Acceptance Table 4. (ERR 1-Dec-2023)

4.2 Uniformity of Dosage Units 〈905〉, Content Uniformity:

Meet the requirements for diclofenac sodium and misoprostol 

5 IMPURITIES 

5.1 Organic Impurities: Misoprostol 

Buffer: Prepare as directed in the Assay for Misoprostol. 

Solvent mixture: Acetonitrile and methanol (26:28) 

Mobile phase: Solvent mixture and Buffer (58:42) 

Diluent: Acetonitrile and water (50:50) 

Standard stock solution: Use the Standard solution prepared as directed in the Assay for Misoprostol. 

Standard solution: 0.001 mg/mL of USP Misoprostol RS prepared as follows. Transfer 5 mL of the Standard stock solution to a 50-mL volumetric ask, and dilute with Diluent to volume. 

Sample solution: Nominally 0.1 mg/mL of misoprostol prepared as follows. Using a quantity of Tablets equivalent to 2 mg of misoprostol, place 1 Tablet at a time on its edge inside a well-folded piece of weighing paper. Tap very carefully the edge of the Tablet with a pestle to separate the Tablet into the outer and inner layers. Remove the inner core containing diclofenac sodium. Fold back the outer layers of the Tablets containing misoprostol, and gently grind them. Transfer the ground outer layers into a 20-mL volumetric ask containing a magnetic stir bar, add 10 mL of acetonitrile, and stir the ask for 2 h. Allow the sample to stand for 10 min, transfer a portion of the solution into a glass centrifuge tube, and centrifuge for 10 min under refrigerated conditions (10°). Transfer 2.5 mL of the supernatant into a 5-mL volumetric ask, and dilute with water to volume. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 200 and 280 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L7 

Temperatures 

Autosampler: 10° 

Column: 35° 

Flow rate: 0.6 mL/min 

Injection volume: 100 µL 

Run time: About 2.5 times the retention time of the misoprostol peak 

System suitability 

Sample: Standard solution at 200 nm 

Suitability requirements 

Tailing factor: NMT 2 

Relative standard deviation: NMT 5.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of 8-epimisoprostol, A-type misoprostol, and any other individual impurity in the portion of Tablets taken: 

Result = (r_u/r_s) × (C_s/C_u) × (1/F) × 100 

r_u = peak response at 200 nm of any impurity from the Sample solution 

r_s = peak response at 200 nm of misoprostol from the Standard solution 

C_s = concentration of USP Misoprostol RS in the Standard solution (mg/mL) 

C_u = nominal concentration of misoprostol in the Sample solution (mg/mL) 

F = relative response factor (see Table 1) 

Calculate the percentage of B-type misoprostol in the portion of Tablets taken: 

Result = (r_u/r_s) × (C_s/C_u) × (1/F) × 100

r_u = peak response at 280 nm of B-type misoprostol from the Sample solution 

r_s = peak response at 200 nm of misoprostol from the Standard solution 

C_s = concentration of USP Misoprostol RS in the Standard solution (mg/mL) 

C_u = nominal concentration of misoprostol in the Sample solution (mg/mL) 

F = relative response factor (see Table 1) 

Acceptance criteria: See Table 1. 

Table 1 

a Methyl(1S*,2R*,3R*)-3-hydroxy-2-[(E)-4-hydroxy-4-methyl-1-octenyl]-5-oxocyclopentaneheptanoate.

b 12-Epimisoprostol, which is a process impurity controlled in the drug substance, and 8-epimisoprostol are not separated by this method and should be integrated together to determine conformance. 

c (E)-Methyl 7-[2-(4-hydroxy-4-methyloct-1-enyl)-5-oxocyclopent-1-enyl]heptanoate. 

d Impurity peak response determined at 280 nm, quantitated against the misoprostol peak response determined at 200 nm.

e Methyl 7-[(1R*,2S*)-2-[(E)-4-hydroxy-4-methyloct-1-enyl]-5-oxocyclopent-3-enyl]heptanoate. 

5.2 Organic Impurities: Diclofenac Sodium 

Mobile phase, Diluent, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay for Diclofenac Sodium. 

Standard solution: 0.004 mg/mL of USP Diclofenac Related Compound A RS in Diluent 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times for diethyl phthalate, diclofenac related compound A, and diclofenac are about 0.6, 0.7, and 1.0, respectively.] 

Suitability requirements 

Resolution: NLT 2.2 between the diethyl phthalate and diclofenac related compound A peaks; NLT 6.5 between the diclofenac related compound A and diclofenac peaks, System suitability solution 

Tailing factor: NMT 2, Standard solution 

Relative standard deviation: NMT 5.0%, Standard solution 

Analysis 

Samples: Sample solution and Standard solution 

Calculate the percentage of diclofenac related compound A and any other individual impurity in the portion of Tablets 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 Diclofenac Related Compound A RS in the Standard solution (mg/mL) 

C_u = nominal concentration of diclofenac sodium in the Sample solution (mg/mL) 

Acceptance criteria 

Diclofenac related compound A: NMT 0.5% 

Any other individual impurity: NMT 0.2% 

Total diclofenac-related impurities: NMT 1.0% 

6 ADDITIONAL REQUIREMENTS 

6.1 Packaging and Storage:

Preserve in tight containers. Store at controlled room temperature. 

6.2 Labeling:

When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

6.3 USP Reference Standards 〈11〉 

USP Diclofenac Sodium RS 

USP Diclofenac Related Compound A RS 

N-(2,6-Dichlorophenyl)indolin-2-one. 

C₁₄H₉Cl₂NO           278.14 

A suitable lter is available as GD/X Syringe Filter, Whatman, catalog no. 6874-2504.