Mesalamine Extended-Release Capsules
If you find any inaccurate information, please let us know by providing your feedback here
This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
1 DEFINITION
Mesalamine Extended-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of mesalamine (C7H7NO3).
2 IDENTIFICATION
A.
Diluent: 0.01 N hydrochloric acid in water
Diluted standard solution: 0.025 mg/mL of USP Mesalamine RS in Diluent
Diluted sample solution: Nominally 0.025 mg/mL of USP Mesalamine RS in Diluent from the Sample solution, prepared as described in the Assay
Acceptance criteria: The UV spectrum of the major peak of the Diluted sample solution corresponds to that of the Diluted standard solution, as obtained in the Assay.
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
Change to read:
PROCEDURE
Buffer: 1.36 g/L of monobasic potassium phosphate in water Solution A: 6.8 g/L of monobasic potassium phosphate in water Solution B: Acetonitrile and Buffer (50:50)
Mobile phase: See Table 1.
Table 1
Time (min) Solution A (%) Solution B (%)
0 100 0
10 100 0
20 60 40
22 60 40
22.1 100 0
30 100 0
Diluent: 0.01 N hy drochloric acid in water
Standard solution: 0.1 mg/mL of USP Mesalamine RS in Diluent
Sample stock solution: Nominally 1.0 mg/mL of mesalamine from Capsules prepared as follows. Transfer a portion of the contents of Capsules (NLT 20), nominally equivalent to 100 mg of mesalamine, to a suitable volumetric flask. Add 50% to up to 80% (RB 1-Jul-2024) of the flask volume of Diluent, and sonicate for NLT (RB 1-Jul-2024) 30 min. Dilute with Diluent to volume, and mix. Centrifuge the solution at 3000 rpm for 10 min.
Sample solution: Nominally 0.1 mg/mL of mesalamine in Diluent, from the Sample stock solution. Pass a portion of the solution through a
suitable filter of 0.45-µm pore size.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.) Mode: LC
Detector: UV 230 nm. For Identification A, use a diode array detector in the range of 200–400 nm. Column: 4.6-mm × 25-cm; 5-µm packing L1
Temperatures Autosampler: 5°
Column: 30°
Flow rate: 0.8 mL/min Injection volume: 20 µL
System suitability
Sample: Standard solution Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 1.0% Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of mesalamine (C H NO ) in the portion of Capsules taken:
Result = (r /r ) × (C /C ) × 100
= peak response of mesalamine from the Sample solution
= peak response of mesalamine from the Standard solution
= concentration of USP Mesalamine RS in the Standard solution (mg/mL)
= nominal concentration of mesalamine in the Sample solution (mg/mL)
Acceptance criteria: 90.0%–110.0%
4 PERFORMANCE TESTS
Change to read:
DISSOLUTION 〈711〉
Test 1
Buffer: 0.05 M pH 7.5 phosphate buffer prepared as follows. Dissolve 6.8 g of monobasic potassium phosphate and 1 g of sodium hy droxide in water to make 1000 mL of solution. Adjust with 10 N sodium hy droxide to a pH of 7.50 ± 0.05.
Medium: Buffer; 900 mL Apparatus 2: 100 rpm
Times: 1, 2, 4, and 8 h
Standard solution: A known concentration of USP Mesalamine RS in Medium
Sample solution: Filter portions of the solution under test suitably diluted with Medium, if necessary.
Analysis: Calculate the percentages of the labeled amount of mesalamine (C H NO ) dissolved at the wavelength of maximum absorbance at about 330 nm by comparing the UV absorbances of the Sample solution with that of the Standard solution.
Tolerances: See Table 2.
Table 2
Time (h) Amount Dissolved (%)
1 5–25
2 30–50
4 60–90
8 NLT 85
The percentages of the labeled amount of mesalamine (C7H7NO3) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. Acid stage
Medium: 0.1 N hy drochloric acid; 750 mL, deaerated. [NOTE—After Acid stage, do not discard the solution. Retain the Capsules in proper
order and proceed immediately as directed for Buffer stage.] Apparatus 1: 100 rpm
Time: 2 h
Standard solution: 0.06 mg/mL of USP Mesalamine RS in Medium
Sample solution: Withdraw a portion of the solution under test and pass through a suitable filter of 0.45-µm pore size and discard the first few milliliters. Add the same volume of Medium to the dissolution vessel.
Instrumental conditions
(See Ultraviolet-Visible Spectroscopy 〈857〉.) Mode: UV
Analytical wavelength: 302 nm Cell: 0.5 cm
Blank: Medium Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of mesalamine (C H NO ) dissolved:
Result = (A /A ) × C × V × (1/L) × 100
= absorbance of the Sample solution
= absorbance of the Standard solution
= concentration of USP Mesalamine RS in the Standard solution (mg/mL)
V = volume of Medium, 750 mL L = label claim (mg/Capsule)
Tolerances: NMT 10%. The percentage of the labeled amount of mesalamine (C7H7NO3) dissolved at the time specified conforms to Dissolution 〈711〉 , Acceptance Table 3.
Buffer stage
Medium: After the Acid stage, immediately add 250 mL of 0.20 M sodium phosphate buffer solution [dissolve about 76 g of sodium phosphate, tribasic (dodecahydrate), in 1000 mL of water; adjust, if necessary, with 10% (v/v) phosphoric acid or 2 N sodium hy droxide to a pH of 12.2] to the dissolution vessels containing the Acid stage medium (750 mL of 0.1 N hydrochloric acid). Adjust, if necessary, with 2 N sodium hy droxide or 2 N hy drochloric acid to a pH of 6.8; deaerated.
Apparatus 1: 100 rpm
Times: 0.5, 1, and 7 h
Solution A: Dissolve 3.4 g of tetrabutylammonium hy drogen sulfate and 1.4 g of sodium acetate (trihydrate) in 1000 mL of water. Adjust with 1 N sodium hydroxide to a pH of 6.6. Add 200 mL of acetonitrile.
Solution B: Dissolve 4.6 g of tetrabutylammonium hy drogen sulfate and 1.9 g of sodium acetate (trihydrate) in 1000 mL of water. Adjust with 1 N sodium hydroxide to a pH of 6.6. Add 650 mL of acetonitrile.
Mobile phase: Solution A and Solution B (90:10)
Standard solution: 0.06 mg/mL of USP Mesalamine RS in Medium
Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size and discard the first few milliliters. Add the same volume of Medium to the dissolution vessel. Dilute with Medium, if necessary, to obtain a solution with a similar concentration as the Standard solution.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.) Mode: LC
Detector: UV 240 nm
Column: 4.6-mm × 10-cm; 3-µm packing L1 Temperatures
Autosampler: 5°
Column: 25°
Flow rate: 1.0 mL/min Injection volume: 10 µL
Run time: NLT 1.7 times the retention time of mesalamine System suitability
Sample: Standard solution
Suitability requirements Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0% Analysis
Samples: Standard solution and Sample solution
Calculate the concentration (Ci) of mesalamine (C7H7NO3) in the sample withdrawn from the vessel at each time point (i):
Result = (r /r ) × C × D
= peak response of mesalamine from the Sample solution
= peak response of mesalamine from the Standard solution
= concentration of USP Mesalamine RS in the Standard solution (mg/mL)
D = dilution factor for the Sample solution
Calculate the percentage of the labeled amount of mesalamine (C H NO ) dissolved at each time point (i):
Result = C × V × (1/L) × 100 Result = [(C × V) + (C × V )] × (1/L) × 100
Result = {(C × V) + [(C + C ) × V ]} × (1/L) × 100
= concentration of mesalamine in the portion of sample withdrawn at time point i (mg/mL)
V = volume of Medium, 1000 mL L = label claim (mg/Capsule)
= volume of the Sample solution withdrawn at each time point from the Medium (mL)
Tolerances: See Table 3.
Table 3
Time Point (i) Time (h) Amount Dissolved (%)
1 0.5 18–43
2 1 35–55
3 7 NLT 80
The percentages of the labeled amount of mesalamine (C H NO ) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Acid stage
Medium: 0.1 N hydrochloric acid; 750 mL Apparatus 1: 100 rpm
Time: 2 h
Standard solution: 0.035 mg/mL of USP Mesalamine RS in Medium. Sonicate to dissolve if necessary.
Sample solution: At the end of the 2-h Acid stage, withdraw 13 mL of the solution under test and pass through a suitable filter of 0.45-µm pore size. Discard the first 5 mL of the filtrate.
Instrumental conditions
(See Ultraviolet-Visible Spectroscopy 〈857〉.) Mode: UV
Analytical wavelength: 302 nm Cell: 1 cm
Blank: Medium
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of mesalamine (C H NO ) dissolved in the Acid stage:
Result = (A /A ) × C × V × (1/L) × 100
= absorbance of the Sample solution
= absorbance of the Standard solution
= concentration of USP Mesalamine RS in the Standard solution (mg/mL)
V = volume of Medium, 750 mL L = label claim (mg/Capsule)
Tolerances: NMT 10%. The percentage of the labeled amount of mesalamine (C H NO ) dissolved at the time specified conforms to Dissolution 〈711〉 , Acceptance Table 3.
Buffer stage
Medium: pH 6.8 phosphate buffer (dissolve 6.8 g of potassium phosphate, monobasic in each liter of water; adjust with 1 N sodium hy droxide solution to a pH of 6.8); 1000 mL
Apparatus 1: 100 rpm
Times: 0.5, 2, and 7 h
Standard solution: 0.03 mg/mL of USP Mesalamine RS in Medium. Sonicate to dissolve if necessary. [NOTE—The Standard solution is stable for 20 h at room temperature.]
Sample solution: After the 2-h Acid stage, discard the Acid stage medium and carefully keep the remaining Capsule contents in the vessels. Add 1000 mL of Buffer stage medium into the vessels and continue with the Buffer stage conditions. At the specified time points, pass 13 mL of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first 5 mL of the filtrate. Dilute
2.0 mL of the filtrate with Buffer stage medium to 25.0 mL. Replace the 13 mL withdrawn at the 0.5 and 2 h time points with an equal volume of the Buffer stage medium. [NOTE—The Sample solution is stable for 11 h at room temperature.]
Instrumental conditions
(See Ultraviolet-Visible Spectroscopy 〈857〉.) Mode: UV
Analytical wavelength: 331 nm Cell: 1 cm
Blank: Medium Analysis
Samples: Standard solution and Sample solution
Calculate the concentration (C ) of mesalamine (C H NO ) in the sample withdrawn from the vessel at each time point (i):
Result = (A /A ) × C × D
= absorbance of the Sample solution
= absorbance of the Standard solution
= concentration of USP Mesalamine RS in the Standard solution (mg/mL)
D = dilution factor for the Sample solution
Calculate the percentage of the labeled amount of mesalamine (C H NO ) dissolved at each time point (i):
Result = C × V × (1/L) × 100 Result = [(C × V) + (C × V )] × (1/L) × 100
Result = {(C × V) + [(C + C ) × V ]} × (1/L) × 100
= concentration of mesalamine in the portion of sample withdrawn at each time point (mg/mL)
V = volume of Medium, 1000 mL L = label claim (mg/Capsule)
= volume of the Sample solution withdrawn at each time point and replaced with the Medium, 13 mL
Tolerances: See Table 4.
Table 4
Time Point (i) Time (h) Amount Dissolved (%)
1 0.5 16–36
2 2 52–72
3 7 NLT 80
The percentages of the labeled amount of mesalamine (C H NO ) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
Test 4: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Medium: 0.05 M pH 7.5 phosphate buffer (dissolve 6.8 g of potassium phosphate monobasic and 1 g of sodium hydroxide in 1000 mL of water; adjust with 10 N sodium hydroxide to a pH of 7.5); 900 mL, deaerated
Apparatus 2: 100 rpm
Times: 1, 2, 4, and 8 h
Standard solution: 0.033 mg/mL of USP Mesalamine RS in Medium. Sonicate to dissolve. [NOTE—The Standard solution is stable for 6 h at room temperature.]
Sample solution: At the specified time points, withdraw a known volume of the solution under test and replace with equal volume of fresh Medium. Pass the withdrawn solution through a suitable filter of 0.45-μm pore size, discarding the first 4 mL of the filtrate. Dilute with Medium to a concentration similar to that of the Standard solution. Pass through a suitable filter of 0.45-μm pore size, discarding the first 5 mL of the filtrate. [NOTE—The unfiltered Sample solution is stable for 16 h at room temperature. After filtration it is recommended to measure the Sample solution absorbance within 2 h.]
Instrumental conditions
(See Ultraviolet-Visible Spectroscopy 〈857〉.) Mode: UV
Analytical wavelength: 330 nm Blank: Medium
Analysis
Samples: Standard solution and Sample solution
Calculate the concentration (C ) of mesalamine (C H NO ) in the sample withdrawn from the vessel at each time point (i):
Result = (A /A ) × C × D
= absorbance of the Sample solution
= absorbance of the Standard solution
= concentration of USP Mesalamine RS in the Standard solution (mg/mL)
D = dilution factor for the Sample solution
Calculate the percentage of the labeled amount of mesalamine (C H NO ) dissolved at each time point (i):
Result = C × V × (1/L) × 100 Result = [(C × V) + (C × V )] × (1/L) × 100
Result = {(C × V) + [(C + C ) × V ]} × (1/L) × 100
Result = {(C × V) + [(C + C + C ) × V ]} × (1/L) × 100
= concentration of mesalamine in the portion of sample withdrawn at each time point (mg/mL)
V = volume of Medium, 900 mL L = label claim (mg/Capsule)
= volume of the Sample solution withdrawn at each time point and replaced with the Medium (mL)
Tolerances: See Table 5.
Table 5
Time Point (i) Time (h) Amount Dissolved (%)
1 1 10–30
2 2 30–50
3 4 62–87
4 8 NLT 85
The percentages of the labeled amount of mesalamine (C H NO ) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
Test 5: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.
Acid stage medium: 0.1 N hydrochloric acid; 750 mL, deaerated.
After the Acid stage, do not discard the solution, retain the Capsules in proper order and proceed immediately as directed for the Buffer stage. The time between completion of acid stage dissolution and starting of buffer stage dissolution should be NMT 30 min.
Solution A: 0.20 M sodium phosphate buffer solution prepared as follows. Dissolve 76 g of sodium phosphate, tribasic in 1000 mL of water. Adjust with 10% (v/v) phosphoric acid or 2 N sodium hy droxide to a pH of 12.2.
Buffer stage medium: pH 6.8 phosphate buffer. (After the Acid stage, add 250 mL of Solution A to the dissolution vessels containing the Acid stage medium. Adjust with 2 N sodium hydroxide or 2 N hydrochloric acid to a pH of 6.8); 1000 mL, deaerated.
Apparatus 1: 100 rpm Times
Acid stage: 2 h
Buffer stage: 0.5, 1, and 7 h. The time in the Buffer stage medium does not include the time in the Acid stage medium.
Acid stage standard solution: 0.05 mg/mL of USP Mesalamine RS in Acid stage medium. Sonicate to dissolve, if necessary. Allow to cool at room temperature. [NOTE—The Acid stage standard solution may be stable for 10 h at room temperature or in a refrigerator. ]
Buffer stage standard solution: 0.375 mg/mL of USP Mesalamine RS in Buffer stage medium. Sonicate to dissolve, if necessary. Allow to cool at room temperature.
Acid stage sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained. Replace the portion withdrawn with the same volume of Acid stage medium in the dissolution vessel. [NOTE—The Acid stage sample solution may be stable for 20 h at room temperature or in a refrigerator.]
Buffer stage sample solution: At the specified time interval, pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained. Replace the portion withdrawn with the same volume of Buffer stage medium in the dissolution vessel.
Solution B: Dissolve 6.9 g of sodium phosphate, monobasic in 1000 mL of water. Adjust with 1 N sodium hy droxide to a pH of 6.2. Mobile phase: Methanol and Solution B (5:95)
Chromatographic system
(See Chromatography 〈621〉, System Suitability.) Mode: LC
Detector: UV 330 nm
Column: 4.6-mm × 25-cm; 5-µm packing L1 Column temperature: 40°
Flow rate: 1.2 mL/min Injection volume: 5 µL
Run time: NLT 1.8 times the retention time of mesalamine System suitability
Samples: Acid stage standard solution and Buffer stage standard solution
Suitability requirements
Tailing factor: NMT 2.0 for both Acid stage standard solution and Buffer stage standard solution
Relative standard deviation: NMT 2.0% for both Acid stage standard solution and Buffer stage standard solution Analysis
Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, and Buffer stage sample solution Calculate the percentage (Q ) of the labeled amount of mesalamine (C H NO ) dissolved in the Acid stage:
Result = (r /r ) × C x V x (1/L) × 100
= peak response of mesalamine from the Acid stage sample solution
= peak response of mesalamine from the Acid stage standard solution
= concentration of USP Mesalamine RS in the Acid stage standard solution (mg/mL)
= volume of Acid stage medium, 750 mL
L = label claim (mg/Capsule)
Calculate the concentration (C ) of mesalamine (C H NO ) in the sample withdrawn from the vessel at each time point (i) during the Buffer stage:
Result = (r /r ) × C
= peak response of mesalamine from the Buffer stage sample solution
= peak response of mesalamine from the Buffer stage standard solution
= concentration of USP Mesalamine RS in the Buffer stage standard solution (mg/mL)
Calculate the percentage of the labeled amount of mesalamine (C H NO ) dissolved at each time point (i) during the Buffer stage:
Result = [C × V × (1/L) × 100] + (Q × V /V )
Result = {[(C × V ) + (C × V )] × (1/L) × 100} + (Q × V /V ) Result = ({(C × V ) + [(C + C ) × V ]} × (1/L) × 100) + (Q × V /V )
= concentration of mesalamine in the portion of sample withdrawn at time point i during the Buffer stage (mg/mL)
= volume of Buffer stage medium, 1000 mL
L = label claim (mg/Capsule)
= the percentage of the labeled amount of mesalamine dissolved in the Acid stage
= volume of the Acid stage sample solution withdrawn at the Acid stage and replaced with Acid stage medium (mL)
= volume of the Acid stage medium, 750 mL
= volume of the Buffer stage sample solution withdrawn at each time point of the Buffer stage and replaced with Buffer stage medium (mL)
Acid stage: NMT 10%. The percentage of the labeled amount of mesalamine (C H NO ) dissolved at the time specified conforms to Dissolution 〈711〉 , Acceptance Table 3.
Buffer stage: See Table 6 .
Table 6
Time Point (i) Time (h) Amount Dissolved (%)
1 0.5 15–35
2 1 35–55
3 7 NLT 80
The percentages of the labeled amount of mesalamine (C7H7NO3) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
Test 6: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6 . Acid stage medium: 0.1 N hy drochloric acid; 750 mL, deaerated, if necessary
Buffer stage medium: pH 6.8 phosphate buffer. (Add 250 mL of 0.2 M potassium phosphate monobasic solution and 112 mL of 0.2 N sodium hydroxide. Dilute with water to 1000 mL. Adjust with 0.2 M potassium phosphate monobasic solution or 0.2 N sodium hydroxide to a pH of 6.8, if necessary.); 1000 mL, deaerated, if necessary.
Apparatus 1: 100 rpm Times
Acid stage: 2 h
Buffer stage: 0.5, 1, and 7 h. The time in the Buffer stage medium does not include the time in the Acid stage medium. Diluent: Acetonitrile, methanol, and water (13:8:79). Adjust with phosphoric acid to a pH of 1.5.
Solution A: Dissolve 1.36 g of potassium phosphate monobasic and 2.2 g of octanesulfonic acid sodium salt in 890 mL of water. Adjust with phosphoric acid to a pH of 2.2.
Mobile phase: Acetonitrile, methanol, and Solution A (13:8:89)
Acid stage standard stock solution: 0.4 mg/mL of USP Mesalamine RS in Diluent. Sonicate to dissolve, if necessary.
Acid stage standard solution: 0.032 mg/mL of USP Mesalamine RS prepared as follows. Transfer a suitable volume of Acid stage standard stock solution to an appropriate volumetric flask and add 6% of the flask volume of Acid stage medium. Dilute with Diluent to volume.
Buffer stage standard stock solution: 0.4 mg/mL of USP Mesalamine RS in Diluent. Sonicate to dissolve, if necessary.
Buffer stage standard solution: 0.032 mg/mL of USP Mesalamine RS prepared as follows. Transfer a suitable volume of Buffer stage standard stock solution to an appropriate volumetric flask and add 8% of the flask volume of Buffer stage medium. Dilute with Diluent to volume.
Acid stage sample solution: Pass a portion of the solution under test through a suitable filter, discarding an appropriate volume of filtrate so that a consistent result can be obtained. Dilute 3 mL of the filtrate with Diluent to 50 mL.
Buffer stage sample solution: After the Acid stage, discard the Acid stage medium and carefully keep the remaining Capsule contents in the
vessels. Add 1000 mL of Buffer stage medium into the vessels and continue with the Buffer stage conditions. At the specified time interval, pass a portion of the solution under test through a suitable filter, discarding an appropriate volume of filtrate so that a consistent result can be obtained. Dilute 4 mL of the filtrate with Diluent to 50 mL. Replace the portion withdrawn with the same volume of Buffer stage medium in the dissolution vessel.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.) Mode: LC
Detector: UV 230 nm
Column: 4.6-mm × 15-cm; 5-µm packing L1 Column temperature: 60°
Flow rate: 1.2 mL/min Injection volume: 20 µL
Run time: NLT 1.7 times the retention time of mesalamine System suitability
Samples: Acid stage standard solution and Buffer stage standard solution
Suitability requirements
Tailing factor: NMT 2.0 for both Acid stage standard solution and Buffer stage standard solution
Relative standard deviation: NMT 2.0% for both Acid stage standard solution and Buffer stage standard solution Analysis
Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, and Buffer stage sample solution Calculate the percentage (Q ) of the labeled amount of mesalamine (C H NO ) dissolved in the Acid stage:
Result = (r /r ) × C × V × D × (1/L) × 100
= peak response of mesalamine from the Acid stage sample solution
= peak response of mesalamine from the Acid stage standard solution
= concentration of USP Mesalamine RS in the Acid stage standard solution (mg/mL)
= volume of Acid stage medium, 750 mL
D = dilution factor of the Acid stage sample solution L = label claim (mg/Capsule)
Calculate the concentration (C ) of mesalamine (C H NO ) in the sample withdrawn from the vessel at each time point (i) during the Buffer stage:
Result = (r /r ) × C × D
= peak response of mesalamine from the Buffer stage sample solution
= peak response of mesalamine from the Buffer stage standard solution
= concentration of USP Mesalamine RS in the Buffer stage standard solution (mg/mL)
D = dilution factor of the Buffer stage sample solution
Calculate the percentage of the labeled amount of mesalamine (C H NO ) dissolved at each time point (i) during the Buffer stage:
Result = [C × V × (1/L) × 100] + Q
Result = {[(C × V ) + (C × V )] × (1/L) × 100} + Q Result = ({(C × V ) + [(C + C ) × V ]} × (1/L) × 100) + Q
= concentration of mesalamine in the portion of sample withdrawn at time point i during the Buffer stage (mg/mL)
= volume of Buffer stage medium, 1000 mL
L = label claim (mg/Capsule)
= the percentage of the labeled amount of mesalamine dissolved in the Acid stage
= volume of the Buffer stage sample solution withdrawn at each time point of the Buffer stage and replaced with Buffer stage medium (mL)
B
Tolerances
Acid stage: NMT 10%. The percentage of the labeled amount of mesalamine (C H NO ) dissolved at the time specified conforms to Dissolution 〈711〉 , Acceptance Table 3.
Buffer stage: See Table 7.
Table 7
Time Point (i) Time (h) Amount Dissolved (%)
1 0.5 7–27
2 1 46–66
3 7 NLT 80
The percentages of the labeled amount of mesalamine (C H NO ) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.▲ (RB 1-Jul-2024)
UNIFORMITY OF DOSAGE UNITS 〈905〉: Meet the requirements
5 IMPURITIES
Change to read:
ORGANIC IMPURITIES
Buffer, Solution A, Solution B, Diluent, and Chromatographic system: Proceed as directed in the Assay. Mobile phase: See Table 8.
Table 8 (RB 1-Jul-2024)
Time (min) Solution A (%) Solution B (%)
0 100 0
10 100 0
40 30 70
45 30 70
46 100 0
55 100 0
Sensitivity solution: 0.5 μg/mL of USP Mesalamine RS in Diluent Standard solution: 0.001 mg/mL of USP Mesalamine RS in Diluent
Sample solution: Nominally 1.0 mg/mL of mesalamine from Capsules prepared as follows. Transfer a portion of the contents of Capsules (NLT 20), nominally equivalent to 25 mg of mesalamine, to a suitable volumetric flask. Add 50% to up to 80% (RB 1-Jul-2024) of the flask volume of Diluent, and sonicate for NLT (RB 1-Jul-2024) 30 min. Dilute with Diluent to volume, and mix. Centrifuge the solution at 3000 rpm for 10 min. Pass a portion of the solution through a suitable filter of 0.45-µm pore size.
System suitability
Samples: Sensitivity solution and Standard solution Suitability requirements
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 any unspecified degradation product in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
= peak response of any unspecified degradation product from the Sample solution
= peak response of mesalamine from the Standard solution
= concentration of USP Mesalamine RS in the Standard solution (mg/mL)
= nominal concentration of mesalamine in the Sample solution (mg/mL)
Acceptance criteria: The reporting threshold is 0.05%. Any unspecified degradation product: NMT 0.13% Total degradation products: NMT 0.5%
6 ADDITIONAL REQUIREMENTS
PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at controlled room temperature.
LABELING: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
USP REFERENCE STANDARDS 〈11〉
USP Mesalamine RS
