Mesalamine Rectal Suspension

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

Mesalamine Rectal Suspension is a suspension of Mesalamine in a suitable aqueous vehicle. It contains NLT 90.0% and NMT 110.0% of the labeled amount of mesalamine (C₇H₇NO₃). It contains one or more suitable preservatives.

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.

3 ASSAY

3.1 PROCEDURE

Buffer: Transfer 7.1 g of anhydrous dibasic sodium phosphate and 6.9 g of monobasic sodium phosphate to a 1000-mL volumetric flask, add 500 mL of water, and swirl to dissolve. Add 7.5 mL of a solution of tetrabutylammonium hydroxide in methanol (1 in 4), dilute with water to volume, and mix.

Mobile phase: Methanol and Buffer (15:85)

System suitability solution: 0.25 mg/mL of 4-aminosalicylic acid and 0.4 mg/mL of USP Mesalamine RS in Mobile phase Standard stock solution: 1 mg/mL of USP Mesalamine RS in Mobile phase

Standard solution: 0.4 mg/mL of USP Mesalamine RS in Mobile phase from the Standard stock solution

Sample solution: Transfer an accurately measured, well-shaken quantity of Rectal Suspension, nominally equivalent to about 100 mg of mesalamine, to a 100-mL volumetric flask. Add 55 mL of Mobile phase, and dissolve by shaking for about 10 min. Dilute with Mobile phase to volume, and mix. Transfer 10.0 mL of this solution to a 25-mL volumetric flask, dilute with Mobile phase to volume, and mix. Pass this solution through a suitable filter of 0.5-µm or finer pore size, and use the filtrate as the Sample solution.

3.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm × 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 15 µL

3.1.2 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between 4-aminosalicylic acid and mesalamine, System suitability solution

Tailing factor: NMT 2.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

3.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of mesalamine (C₇H₇NO₃) in the portion of Rectal Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of mesalamine from the Sample solution

r_S = peak response of mesalamine from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 OTHER COMPONENTS

4.1 CONTENT OF SODIUM BENZOATE (if present)

Mobile phase: Transfer 390 mg of ammonium acetate to a 1000-mL volumetric flask, add 100 mL of water, and dissolve by swirling. Add 6 mL of glacial acetic acid and 300 mL of methanol, dilute with water to volume, and mix. Pass this solution through a filter of 0.5-µm or finer pore size.

Standard solution: 1 mg/mL of sodium benzoate in water. To 5.0 mL of this solution add 40 mL of methanol, and dilute with water to 100 mL. Pass this solution through a filter of 0.5-µm or finer pore size.

Sample solution: Transfer about 5 g of well-shaken Rectal Suspension to a 100-mL volumetric flask. Add 40 mL of methanol, dilute with water to volume, and mix. Pass the solution through a filter of 0.5-µm or finer pore size.

4.1.1 Chromatographic system

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25.0-cm; packing L7

Flow rate: 1.5 mL/min

Injection volume: 15 µL

4.1.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 2.0%

4.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage (w/w) of sodium benzoate in the Rectal Suspension taken:

Result = (r_U/r_S) × C_S × (10/W)

r_U = peak response of sodium benzoate from the Sample solution

r_S = peak response of sodium benzoate from the Standard solution

C_S = concentration of sodium benzoate in the Standard solution (mg/mL)

W = weight of Rectal Suspension taken (g)

Acceptance criteria: 0.05%–0.125%

5 PERFORMANCE TESTS

Change to read:

5.1 UNIFORMITY OF DOSAGE UNITS 〈905〉

Meets the requirements (CN 1-Aug-2023)

Procedure for content uniformity

Buffer: Transfer 7.1 g of anhydrous dibasic sodium phosphate and 6.9 g of monobasic sodium phosphate to a 1000-mL volumetric flask, add 500 mL of water, and swirl to dissolve. Add 7.5 mL of a solution of tetrabutylammonium hydroxide in methanol (1 in 4), dilute with water to volume, and mix.

Mobile phase: Methanol and Buffer (15:85)

System suitability solution: 0.25 mg/mL of 4-aminosalicylic acid and 0.4 mg/mL of USP Mesalamine RS in Mobile phase

Standard stock solution: Transfer about 100 mg of USP Mesalamine RS to a 50-mL volumetric flask, add 15 mL of 2 N hydrochloric acid, and dissolve by swirling. Dilute with 2 N hydrochloric acid to volume, and mix.

Standard solution: Add 5 mL of 2 N sodium hydroxide to 5.0 mL of the Standard stock solution, and dilute with Mobile phase to 25 mL. Pass this solution through a filter of 0.5-µm or finer pore size.

Sample stock solution: Transfer, with the aid of 2 N hydrochloric acid, the contents of a container of Rectal Suspension to a 200-mL volumetric flask. Add 2 N hydrochloric acid to obtain about 160 mL of solution, and shake for 10 min. Dilute with 2 N hydrochloric acid to volume, and mix.

Sample solution: Transfer a suitable volume of the Sample stock solution, nominally equivalent to 40 mg of mesalamine, to a 100-mL volumetric flask. Add a volume of 2 N hydrochloric acid, equal to the added volume of the Sample stock solution, dilute with Mobile phase to volume, and mix. Pass this solution through a suitable filter of 0.5-µm or finer pore size.

5.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.) Mode: LC

Detector: UV 254 nm

Column: 4-mm × 30-cm; packing L1 Flow rate: 2 mL/min

Injection volume: 15 µL

5.1.2 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between 4-aminosalicylic acid and mesalamine, System suitability solution

Tailing factor: NMT 2.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

5.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of mesalamine (C H NO ) in the container of Rectal Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of mesalamine from the Sample solution

r_S = peak response of mesalamine from the Standard solution

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

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

(CN 1-Aug-2023)

6 IMPURITIES

6.1 ORGANIC IMPURITIES

Mobile phase: Dissolve 1.36 g of monobasic potassium phosphate and 2.2 g of sodium 1-octanesulfonate in 890 mL of water, and adjust with phosphoric acid to a pH of 2.2. Pass through a filter of 0.5-µm or finer pore size. To the filtrate add 80 mL of methanol and 30 mL of acetonitrile.

Standard solution: 1 µg/mL each of USP Mesalamine RS and 3-aminosalicylic acid in Mobile phase

Sample solution: Transfer a volume of Rectal Suspension, previously well shaken, nominally equivalent to 100 mg of mesalamine, to a beaker. Add water to give a volume of about 80 mL, and adjust with phosphoric acid to a pH of 2.0. Sonicate briefly to dissolve, transfer to a 100-mL volumetric flask, dilute with water to volume, and mix.

6.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

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

Flow rate: 1.2 mL/min

Injection volume: 20 µL

Run time: 3 times the retention time of mesalamine

6.1.2 System suitability

Sample: Standard solution

[NOTE—The relative retention times for mesalamine and 3-aminosalicylic acid are about 1.0 and 1.3, respectively.]

Suitability requirements

Resolution: NLT 2 between mesalamine and 3-aminosalicylic acid

6.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Rectal Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

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

r_S = peak response of mesalamine from the Standard solution

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

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

Acceptance criteria

Individual impurities: NMT 0.2% Total impurities: NMT 1.0%

7 SPECIFIC TESTS

PH 〈791〉

Sample solution: Dilute the Rectal Suspension 1 to 10 with water. Acceptance criteria: 3.5–5.5

8 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers.

USP REFERENCE STANDARDS 〈11〉

USP Mesalamine RS