Diluted Isosorbide Dinitrate
;)
D-Glucitol,1,4:3,6-dianhydro-,dinitrate.
1,4:3,6-Dianhydro-D-glucitol dinitrate [87-33-2].
»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 1.0percent of a suitable stabilizer,such as Ammonium Phosphate.It contains not less than 95.0percent and not more than 105.0percent of the labeled amount of C6H8N2O8.It usually contains approximately 25percent of isosorbide dinitrate.
Caution—Exercise 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.
Identification—
Transfer to a medium-porosity,sintered-glass filtering crucible a quantity of it,equivalent to about 50mg of isosorbide dinitrate,and pass three 5-mLportions 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 16hours:the IRabsorption spectrum of a 1in 40solution 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.
,with the aid of a gentle current of air,and dry the residue in vacuum over calcium chloride at room temperature for 16hours:the IRabsorption spectrum of a 1in 40solution 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 á731ñ—
Dry it in vacuum over calcium chloride at room temperature for 16hours:it loses not more than 1.0%of its weight.
Heavy metals,Method IIá231ñ:
0.001%.
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
Assay—
Buffer solution—
Dissolve 15.4g of ammonium acetate in water,add 11.5mLof glacial acetic acid,dilute with water to 1000mL,and mix to obtain a solution having a pHof about 4.7.
Mobile phase—
Mix 350mLof water,100mLof Buffer solution,and 550mLof methanol.Cool to room temperature,dilute with water to 1000mL,mix,degas,and filter.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
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 5minutes,and shake for 30minutes.Dilute with methanol to volume to obtain a solution having a concentration of about 3mg 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 125mg of recently mixed USP Diluted Isosorbide Dinitrate RS,accurately weighed,to a 50-mLvolumetric flask,add about 30mLof Mobile phase,shake for 30minutes,dilute with Mobile phaseto volume,and mix.Pipet 10mLof the resulting solution into a 25-mLvolumetric flask,and add 4.0mLof Internal standard solutionand 4mLof dilute Buffer solution(1in 10).Cool to room temperature,dilute with Mobile phaseto volume,and mix to obtain a solution having a known concentration of about 0.25mg of isosorbide dinitrate per mL,based on the quantity of USP Diluted Isosorbide Dinitrate RSweighed 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 30mg of isosorbide dinitrate,to a 50-mLvolumetric flask.Proceed as directed for Standard preparation,beginning with “add about 30mLof Mobile phase.”
Chromatographic system (see Chromatography á621ñ)—
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 1mLper 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%.[NOTE—The relative retention times are about 0.75for isosorbide dinitrate and 1.0for nitroglycerin.The relative retention times for isosorbide mononitrates,if present,are about 0.38.]
Procedure—
Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C6H8N2O8in the portion of Diluted Isosorbide Dinitrate taken by the formula:
125C(RU/RS),
in which Cis the concentration,in mg per mL,of isosorbide dinitrate from USP Diluted Isosorbide Dinitrate RStaken for the Standard preparation;and RUand RSare the peak response ratios obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1085
Pharmacopeial Forum:Volume No.27(3)Page 2564
Phone Number:1-301-816-8305