Isosorbide Mononitrate 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

Isosorbide Mononitrate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of isosorbide mononitrate (C₆H₉NO₆ ).

2 IDENTIFICATION

Change to read:

A. Thin-Layer Chromatographic Identification Test 〈201〉

Standard solution: 0.5 mg/mL of isosorbide mononitrate in absolute alcohol from USP Diluted Isosorbide Mononitrate RS

Sample stock solution: Nominally 2.4 mg/mL of isosorbide mononitrate prepared as follows. Finely powder NLT 20 Tablets and transfer a suitable portion of the powder to a suitable container. Add a suitable volume of absolute alcohol, sonicate for 10 min, and centrifuge. Use the supernatant.

Sample solution: Nominally 0.48 mg/mL of isosorbide mononitrate in absolute alcohol from the Sample stock solution

Chromatographic system

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture (USP 1-May-2024)

Application volume: 20 μL

Developing solvent system: Chloroform and methanol (95:5)

Spray reagent: Dissolve 1 g of soluble starch in 100 mL of boiling water. Cool and add 0.5 g of potassium iodide.

Analysis

Samples: Standard solution and Sample solution

Examine the plate under short-wave UV light, marking any observed spots. Visualize nitrates on the plate by spraying with Spray reagent

and illuminating with short-wave UV light for about 10 min.

Acceptance criteria: Isosorbide mononitrate and other nitrates appear as a violet spot on a white-to-light violet background.

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

Mobile phase: Methanol and water (30:70)

System suitability solution: 0.5 μg/mL each of isosorbide mononitrate and isosorbide mononitrate related compound A in water (USP 1-

May-2024) from USP Diluted Isosorbide Mononitrate RS and USP Diluted Isosorbide Mononitrate Related Compound A RS

Standard solution: 0.1 mg/mL of isosorbide mononitrate in water from USP Diluted Isosorbide Mononitrate RS. Pass a portion of the solution

through a suitable filter of 0.45-μm or finer pore size, and use the filtrate.

Sample solution: Nominally 0.1 mg/mL of isosorbide mononitrate prepared as follows. Finely powder NLT 20 Tablets and transfer a suitable portion of the powder to a suitable volumetric flask. Add 50% of the final volume of water, and sonicate for about 10 min. Dilute with water to volume. Pass a portion of the solution through a suitable filter of 0.45-μm or finer pore size, and use the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; 5-μm (USP 1-May-2024) packing L1

Flow rate: 1 mL/min (USP 1-May-2024)

Injection volume: 50 μL

Run time: NLT 6 times the retention time of isosorbide mononitrate (USP 1-May-2024)

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for isosorbide mononitrate related compound A and isosorbide mononitrate are 0.9 and 1.0,

respectively.] (USP 1-May-2024)

Suitability requirements

Resolution: NLT 1.5 between isosorbide mononitrate related compound A and isosorbide mononitrate, System suitability solution

Relative standard deviation: NMT 1.0%, (USP 1-May-2024) Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of isosorbide mononitrate (C₆H₉NO₆) in the portion of Tablets taken:

Result = (r_U/r_S)  x (C_S/C_U ) × 100

r_U = peak response of isosorbide mononitrate from the Sample solution

r_S = peak response of isosorbide mononitrate from the Standard solution

C_S = concentration of isosorbide mononitrate in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Medium: Water; 900 mL, deaerated

Apparatus 2: 50 rpm

Time: 15 min

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.02 mg/mL of isosorbide mononitrate from USP Diluted Isosorbide Mononitrate RS in Medium (USP 1-May-2024)

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. Discard the first few milliliters of the filtrate.

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 1.5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of isosorbide mononitrate (C₆H₉NO₆) dissolved:

Result = (r_U/r_S) × C_S × V × (1/L) × 100

r_U = peak response of isosorbide mononitrate from the Sample solution

r_S = peak response of isosorbide mononitrate from the Standard solution

C_S = concentration of isosorbide mononitrate in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of isosorbide mononitrate (C₆H₉NO₆) is dissolved

Change to read:

Uniformity of Dosage Units 〈905〉: Meet the requirements

(USP 1-May-2024)

4 IMPURITIES

Add the following:

Limit of Nitrate

[Note—Use water with a resistivity of NLT 18 megohm-cm to prepare the solutions.]

Mobile phase: 20 mM potassium hydroxide in water. [Note—Mobile phase can be generated electrolytically using an automatic eluant

generator.]

Sensitivity solution: 0.5 μg/mL of USP Potassium Nitrate RS in water

Standard solution: 1.0 μg/mL of USP Potassium Nitrate RS in water

Sample solution: Nominally 200 μg/mL of isosorbide mononitrate prepared as follows. Finely powder NLT 20 Tablets and transfer a suitable portion of the powder to a suitable volumetric flask. Add water to about 80% of the final flask volume. Sonicate for about 10 min with intermittent shaking, cool to ambient temperature, and dilute with water to volume. Centrifuge a portion of the solution and use the clear supernatant.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Conductivity with suppression

Columns

Guard: 4.0-mm × 0.5-cm; 5.0-μm packing L91

Analytical: 4.0-mm × 15-cm; 5.0-μm packing L91

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 100 μL

Run time: NLT 2 times the retention time of nitrate

System suitability

Sample: Sensitivity solution

Suitability requirements

Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of nitrate as potassium nitrate in the portion of Tablets taken:

Result = (r_U/r_S)  x (C_S/C_U ) × 100

r_U = peak response of the nitrate ion from the Sample solution

r_S = peak response of the nitrate ion from the Standard solution

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

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

Acceptance criteria: NMT 0.5%, calculated as potassium nitrate (USP 1-May-2024)

Change to read:

Organic Impurities

[Note—It is recommended to use GC-grade methanol to prepare the solutions.]

Sensitivity solution: 3 μg/mL of isosorbide mononitrate in methanol prepared as follows. Transfer a suitable amount of USP Diluted

Isosorbide Mononitrate RS to a suitable volumetric flask. Add methanol to about 80% of the final flask volume and sonicate for 30 min with intermittent shaking. Dilute with methanol to volume. Centrifuge a portion of the solution and use the clear supernatant.

Standard solution: 6 μg/mL of isosorbide mononitrate, 30 μg/mL of isosorbide, and 15 μg/mL each of isosorbide mononitrate related compound A (ERR 1-May-2024) and isosorbide dinitrate in methanol prepared as follows. Transfer a suitable amount of USP Diluted Isosorbide Mononitrate RS, USP Diluted Isosorbide Mononitrate Related Compound A RS, and USP Diluted Isosorbide Dinitrate RS to a suitable volumetric flask. Add methanol to about 80% of the final flask volume and sonicate for 30 min with intermittent shaking. Add an appropriate amount of USP Isosorbide RS and dilute with methanol to volume. Centrifuge a portion of the solution and use the clear supernatant.

Sample solution: Nominally 3 mg/mL of isosorbide mononitrate in methanol prepared as follows. Finely powder NLT 20 Tablets and transfer a suitable portion of the powder to a suitable volumetric flask. Add methanol to about 80% of the final flask volume. Sonicate for 30 min with intermittent shaking, cool to ambient temperature, and dilute with methanol to volume. Centrifuge a portion of the solution and use the clear supernatant.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.53-mm × 30-m fused-silica capillary; coated with a 1.5-μm

lm of phase G2

Temperatures

Injection port: 150°

Column: 125°, isothermal

Detector: 275°

Carrier gas: Hydrogen

Flow rate: 180 cm/s (linear velocity)

Injection volume: 1 μL

Injection type: Split, split ratio 1:6

Run time: NLT 3 times the retention time of isosorbide mononitrate

System suitability

Samples: Sensitivity solution and Standard solution

[Note—See Table 1 for the relative retention times.]

Suitability requirements

Relative standard deviation: NMT 5% each for isosorbide mononitrate, isosorbide, isosorbide mononitrate related compound A (ERR 1-

May-2024) , and isosorbide dinitrate, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of isosorbide, isosorbide mononitrate related compound A (ERR 1-May-2024) , and isosorbide dinitrate in the portion of Tablets taken:

Result = (r_U/r_S)  x (C_S/C_U ) × 100

r_U = peak response of isosorbide, isosorbide mononitrate related compound A (ERR 1-May-2024) , or isosorbide dinitrate from the Sample solution

r_S = peak response of isosorbide, isosorbide mononitrate related compound A (ERR 1-May-2024) , or isosorbide dinitrate from the Standard solution

C_S = concentration of isosorbide, isosorbide mononitrate related compound A (ERR 1-May-2024) , or isosorbide dinitrate in the Standard solution (mg/mL)

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

Calculate the percentage of any unspecified degradation product in the portion of Tablets taken:

Result = (r_U/r_S)  x (C_S/C_U ) × 100

r_U = peak response of each unspecified degradation product from the Sample solution

r_S = peak response of isosorbide mononitrate from the Standard solution

C_S = concentration of isosorbide mononitrate in the Standard solution (mg/mL)

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

Acceptance criteria: See Table 1. The reporting threshold is 0.1%.

Table 1

(USP 1-May-2024)

5 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in tight containers and store at a temperature between 20° and 30°, excursions permitted between 15° and 30°. (USP 1-May-2024)

Change to read:

USP Reference Standards 〈11〉

USP Isosorbide RS

[Note—USP Diluted Isosorbide Dinitrate RS, USP Diluted Isosorbide Mononitrate RS, and USP Diluted Isosorbide Mononitrate Related Compound A RS are dry mixtures of an active component and suitable excipients to permit safe handling. For quantitative applications, calculate the concentration of the active component based on the content stated on the label.]

USP Diluted Isosorbide Dinitrate RS

USP Diluted Isosorbide Mononitrate RS

USP Diluted Isosorbide Mononitrate Related Compound A RS

1,4:3,6-Dianhydro-d-glucitol 2-nitrate in lactose. (USP 1-May-2024)

C₆H₉NO₆ 191.14

USP Potassium Nitrate RS (USP 1-May-2024)