Isosorbide Mononitrate Tablets

General Notices

Action and use

Nitric oxide analogue; angina pectoris.

Definition

Isosorbide Mononitrate Tablets contain Diluted Isosorbide Mononitrate.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of isosorbide mononitrate, C6H9NO6

95.0 to 105.0% of the stated amount.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Extract a quantity of the powdered tablets containing 10 mg of isosorbide mononitrate with 10 mL of ethanol (96%) and filter.
(2) 0.1% w/v solution of isosorbide mononitrate BPCRS in ethanol (96%).
chromatographic conditions
(a) Use a TLC silica gel plate (Merck silica gel 60 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry it in a current of air, spray with diphenylamine solution R1 and irradiate for 15 minutes with ultraviolet light (254 and 365 nm).
mobile phase

5 volumes of methanol and 95 volumes of dichloromethane.

confirmation

The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).

B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).

Tests

Inorganic nitrates

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Shake a quantity of the powdered tablets containing 0.1 g of isosorbide mononitrate with 5 mL of ethanol (96%) and filter.
(2) Dissolve 10 mg of potassium nitrate in 1 mL of water and dilute to 100 mL with ethanol (96%).
chromatographic conditions
(a) Use a TLC silica gel plate (Analtech silica gel H plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate thoroughly dry it in a current of air until the acetic acid is completely removed. Spray copiously with freshly prepared potassium iodide and starch solution. Expose the plate to ultraviolet light (254 nm) for 15 minutes and examine in daylight.
mobile phase

15 volumes of glacial acetic acid, 30 volumes of acetone and 60 volumes of toluene.

limits

In the chromatogram obtained with solution (1) any spot corresponding to potassium nitrate is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%, calculated as potassium nitrate).

Isosorbide dinitrate and isosorbide 2-nitrate

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Add 15 mL of mobile phase to a quantity of the powdered tablets containing 50 mg of isosorbide mononitrate, mix with the aid of ultrasound for 15 minutes and dilute to 25 mL with the same solvent. Filter through a membrane filter with a nominal pore size not greater than 0.45 µm and use the filtrate.
(2) 0.001% w/v of isosorbide 2-nitrate BPCRS in the mobile phase.
(3) 0.001% w/v of isosorbide dinitrate BPCRS in the mobile phase.
(4) 0.001% w/v each of isosorbide mononitrate BPCRS and isosorbide 2-nitrate BPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octyldecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 2 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 20 µL of each solution.
mobile phase

30 volumes of methanol and 70 volumes of water.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks corresponding to isosorbide mononitrate and isosorbide 2-nitrate is at least 2.4.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to isosorbide 2-nitrate is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);

the area of any peak corresponding to isosorbide dinitrate is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.5%).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Add 70 mL of mobile phase to a quantity of the powdered tablets containing 50 mg of isosorbide mononitrate, mix with the aid of ultrasound for 15 minutes, dilute to 100 mL with the same solvent and centrifuge. Dilute 1 volume of the supernatant liquid to 5 volumes with mobile phase and filter through a membrane filter with a nominal pore size not greater than 0.45 µm.
(2) Add 20 mL of mobile phase to a quantity of isosorbide mononitrate BPCRS containing 25 mg of isosorbide mononitrate, mix with the aid of ultrasound for 15 minutes, dilute to 25 mL with the same solvent and centrifuge. Dilute 1 volume of the supernatant liquid to 10 volumes with the mobile phase and filter through a membrane filter with a nominal pore size not greater than 0.45 µm.
(3) 0.001% w/v each of isosorbide mononitrate BPCRS and isosorbide 2-nitrate BPCRS in the mobile phase.
chromatographic conditions

The chromatographic conditions described under Isosorbide dinitrate and isosorbide 2-nitrate may be used.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks corresponding to isosorbide mononitrate and isosorbide 2-nitrate is at least 2.4.

determination of content

Calculate the content of C6H9NO6 in the tablets from the chromatograms obtained and using the declared content of C6H9NO6 in isosorbide mononitrate BPCRS.