Drug release 
724
—
Medium:
0.05 M pH 7.5 phosphate buffer prepared by dissolving 6.8 g of monobasic potassium phosphate and 1 g of sodium hydroxide in water to make 1000 mL of solution, and adjusting with 10 N sodium hydroxide to a pH of 7.50 ± 0.05; 900 mL.
Apparatus 2:
100 rpm.
Times:
1, 2, 4, and 8 hours.
Procedure—
Determine the amount of C
7H
7NO
3 dissolved from UV absorbances at the wavelength of maximum absorbance at about 330 nm on filtered portions of the solution under test suitably diluted with
Medium, if necessary, in comparison with a Standard solution having a known concentration of
USP Mesalamine RS in the same
Medium.
Tolerances—
The percentages of the labeled amount of C
7H
7NO
3 dissolved at the times specified conform to
Acceptance Table 1.
| Time (hours) |
Amount dissolved |
| 1 |
between 5% and 25% |
| 2 |
between 30% and 50% |
| 4 |
between 60% and 90% |
| 8 |
not less than 85% |
Dissolution 711—
Medium:
0.05 M pH 7.5 phosphate buffer prepared by dissolving 6.8 g of monobasic potassium phosphate and 1 g of sodium hydroxide in water to make 1000 mL of solution, and adjusting with 10 N sodium hydroxide to a pH of 7.50 ± 0.05; 900 mL.
Apparatus 2:
100 rpm.
Times:
1, 2, 4, and 8 hours.
Procedure—
Determine the amount of C
7H
7NO
3 dissolved from UV absorbances at the wavelength of maximum absorbance at about 330 nm on filtered portions of the solution under test suitably diluted with
Medium, if necessary, in comparison with a Standard solution having a known concentration of
USP Mesalamine RS in the same
Medium.
Tolerances—
The percentages of the labeled amount of C
7H
7NO
3 dissolved at the times specified conform to
Acceptance Table 2.
| Time (hours) |
 Amount dissolved |
| 1 |
between 5% and 25% |
| 2 |
between 30% and 50% |
| 4 |
between 60% and 90% |
| 8 |
not less than 85% |
(Official April 1, 2006)
Assay—
Buffer—
Dissolve 6.8 g of monobasic potassium phosphate and 1.65 g of sodium hydroxide in 800 mL of water, adjust with 1 N sodium hydroxide to a pH of 7.5, dilute with water to 1000 mL, and mix.
Mobile phase A—
Dissolve 3.4 g of tetrabutylammonium hydrogen sulfate and 1.4 g of sodium acetate trihydrate in 1000 mL of water, and adjust with 1 N sodium hydroxide to a pH of 6.6. Add 200 mL of acetonitrile, mix, and pass through a filter having a 0.5-µm or finer porosity. Make any necessary adjustments (see
System Suitability under
Chromatography 621).
[NOTE—Increasing the proportion of acetonitrile decreases the retention times. Prepare fresh daily.
]
Mobile phase B—
Dissolve 4.6 g of tetrabutylammonium hydrogen sulfate and 1.9 g of sodium acetate trihydrate in 1000 mL of water, and adjust with 1 N sodium hydroxide to a pH of 6.6. Add 650 mL of acetonitrile, mix, and pass through a filter having a 0.5-µm or finer porosity. Make any necessary adjustments (see
System Suitability under
Chromatography 621).
[NOTE—Prepare fresh daily.
]
Internal standard solution—
Prepare a solution in Buffer containing about 35 mg of sodium benzoate per mL.
Standard preparation—
Transfer about 50 mg of
USP Mesalamine RS, accurately weighed, to a 100-mL volumetric flask, add 4.0 mL of
Internal standard solution, mix, dilute with
Buffer to volume, and mix. Transfer 5.0 mL of this solution to a 25-mL volumetric flask, dilute with
Buffer to volume, and mix.
Assay preparation—
Transfer, as completely as possible, the contents of not fewer than 20 Capsules to a suitable tared container, and determine the average weight of the contents of a Capsule. Finely powder the Capsule contents so that the powder thus obtained passes through a No. 40 sieve (see
Powder Fineness 811). Transfer an accurately weighed portion of the powder, equivalent to about 250 mg of mesalamine, to a 500-mL volumetric flask, add 20.0 mL of
Internal standard solution and about 300 mL of
Buffer, and shake by mechanical means for 1 hour. Dilute with
Buffer to volume, and mix. Transfer 5.0 mL of this solution to a 25-mL volumetric flask, dilute with
Buffer to volume, mix, and pass about 10 mL of this solution through a filter having a 0.5-µm or finer porosity. Use the filtrate as the
Assay preparation.
Chromatographic system
(see
Chromatography 621)—The liquid chromatograph is equipped with a 240-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1, and is programmed to provide variable mixtures of
Mobile phase A and
Mobile phase B. The flow rate is about 1.5 mL per minute. The system is equilibrated with
Mobile phase A. Five minutes after the injection of the
Standard preparation and the
Assay preparation, the proportion of
Mobile phase B is increased linearly from 0% to 100% over a period of 2 minutes, and held for 8 minutes. The proportion of
Mobile phase A is then increased linearly from 0% to 100% over a period of 2 minutes and held for 3 minutes. Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the relative retention times are about 0.6 for mesalamine and 1.0 for sodium benzoate, the resolution,
R, between mesalamine and sodium benzoate; is not less than 2.5; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of mesalamine (C
7H
7NO
3) in the portion of Capsule contents taken by the formula:
2500C(RU / RS),
in which
C is the concentration, in mg per mL, of
USP Mesalamine RS in the
Standard preparation; and
RU and
RS are the peak response ratios of the mesalamine peak to the sodium benzoate peak obtained from the
Assay preparation and the
Standard preparation, respectively.
1 and 1240 cm