Diluted Isosorbide Dinitrate
» Diluted Isosorbide Dinitrate is a dry mixture of isosorbide dinitrate (C6H8N2O8) with Lactose, Mannitol, or suitable inert excipients to permit safe handling. It may contain up to 1.0 percent of a suitable stabilizer, such as Ammonium Phosphate. It contains not less than 95.0 percent and not more than 105.0 percent of the labeled amount of C6H8N2O8. It usually contains approximately 25 percent of isosorbide dinitrate.
[CautionExercise proper precautions in handling undiluted isosorbide dinitrate, which is a powerful explosive and can be exploded by percussion or excessive heat. Only exceedingly small amounts should be isolated. ]
Packaging and storage Preserve in tight containers.
USP Reference standards 11
Identification Transfer to a medium-porosity, sintered-glass filtering crucible a quantity of it, equivalent to about 50 mg of isosorbide dinitrate, and pass three 5-mL portions of acetone through it. Evaporate the combined extracts at a temperature not exceeding 35, with the aid of a gentle current of air, and dry the residue in vacuum over calcium chloride at room temperature for 16 hours: the IR absorption spectrum of a 1 in 40 solution of the residue so obtained, in chloroform, determined in a 0.1-mm cell, exhibits maxima only at the same wavelengths as that of a similar preparation from the residue obtained from USP Diluted Isosorbide Dinitrate RS.
Loss on drying 731 Dry it in vacuum over calcium chloride at room temperature for 16 hours: it loses not more than 1.0% of its weight.
Heavy metals, Method II 231: 0.001%.
Buffer solution Dissolve 15.4 g of ammonium acetate in water, add 11.5 mL of glacial acetic acid, dilute with water to 1000 mL, and mix to obtain a solution having a pH of about 4.7.
Mobile phase Mix 350 mL of water, 100 mL of Buffer solution, and 550 mL of methanol. Cool to room temperature, dilute with water to 1000 mL, mix, degas, and filter. Make adjustments if necessary (see System Suitability under Chromatography 621).
Internal standard solution Transfer a quantity of diluted nitroglycerin to a suitable volumetric flask, add about 60% of the flask volume of methanol, sonicate for 5 minutes, and shake for 30 minutes. Dilute with methanol to volume to obtain a solution having a concentration of about 3 mg of nitroglycerin per mL, and mix. Allow any undissolved material to settle, filter, and store the filtrate in an airtight container.
Standard preparation Transfer about 125 mg of recently mixed USP Diluted Isosorbide Dinitrate RS, accurately weighed, to a 50-mL volumetric flask, add about 30 mL of Mobile phase, shake for 30 minutes, dilute with Mobile phase to volume, and mix. Pipet 10 mL of the resulting solution into a 25-mL volumetric flask, and add 4.0 mL of Internal standard solution and 4 mL of dilute Buffer solution (1 in 10). Cool to room temperature, dilute with Mobile phase to volume, and mix to obtain a solution having a known concentration of about 0.25 mg of isosorbide dinitrate per mL, based on the quantity of USP Diluted Isosorbide Dinitrate RS weighed and the labeled content of isosorbide dinitrate. Pass a portion of this solution through a 0.45-µm filter.
Assay preparation Transfer an accurately weighed quantity of recently mixed Diluted Isosorbide Dinitrate, equivalent to about 30 mg of isosorbide dinitrate, to a 50-mL volumetric flask. Proceed as directed for Standard preparation, beginning with add about 30 mL of Mobile phase.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 220-nm detector and a 4-mm × 25-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the resolution, R, between isosorbide dinitrate and nitroglycerin is not less than 2.0; and the relative standard deviation for replicate injections determined from the peak response ratios is not more than 2%. [noteThe relative retention times are about 0.75 for isosorbide dinitrate and 1.0 for nitroglycerin. The relative retention times for isosorbide mononitrates, if present, are about 0.38. ]
Procedure Separately inject equal volumes (about 20 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 C6H8N2O8 in the portion of Diluted Isosorbide Dinitrate taken by the formula:
125C(RU / RS)in which C is the concentration, in mg per mL, of isosorbide dinitrate from USP Diluted Isosorbide Dinitrate RS taken for the Standard preparation; and RU and RS are the peak response ratios obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3587Pharmacopeial Forum: Volume No. 27(3) Page 2564