Isosorbide Concentrate
;)
D-Glucitol,1,4:3,6-dianhydro-.
1,4:3,6-Dianhydro-D-glucitol [652-67-5].
»Isosorbide Concentrate is an aqueous solution containing,in each 100g,not less than 70.0g and not more than 80.0g of C6H10O4.
Packaging and storage—
Preserve in tight,light-resistant containers.
Labeling—
The label states that this article is not intended for direct administration to humans or animals.
Identification—
[NOTE—Isosorbide is hygroscopic.Take precautions to protect isolated isosorbide crystals from atmospheric moisture.]
A:
Dry a portion of it in an evaporating dish over phosphorus pentoxide at 70
and at a pressure of 50mm of mercury for 48hours,changing the phosphorus pentoxide after 24hours.Scratch the bottom of the dish with a glass rod or seed with a crystal of isosorbide,if necessary,to initiate crystallization:the crystals so obtained melt between 60and 63when tested by the procedure for Class Isubstances (see Melting Range or Temperature á741ñ).
and at a pressure of 50mm of mercury for 48hours,changing the phosphorus pentoxide after 24hours.Scratch the bottom of the dish with a glass rod or seed with a crystal of isosorbide,if necessary,to initiate crystallization:the crystals so obtained melt between 60and 63when tested by the procedure for Class Isubstances (see Melting Range or Temperature á741ñ).
B:
The IRabsorption spectrum of a potassium bromide dispersion of the crystals obtained as directed in Identificationtest Aexhibits maxima and minima only at the same wavelengths as that of a similar preparation of USP Isosorbide RS.
Specific rotation á781Sñ:
between +44.5and +47.0.
and +47.0.
Test solution:
80mg of isosorbide per mL,in water.
Water,Method Iá921ñ:
between 24.0%and 26.0%.
Residue on ignition á281ñ:
not more than 0.01%.
Heavy metals,Method IIá231ñ:
not more than 5ppm,calculated on the anhydrous basis.
Periodate consumption—
Dilute about 15g,accurately weighed,with 25mLof water,and add 50.0mLof a solution prepared by dissolving 5.4g of periodic acid in 100mLof water and adding 1900mLof glacial acetic acid.Allow to stand for 1hour.Add 20mLof potassium iodide TS,and titrate with 0.1Nsodium thiosulfate VSto the disappearance of the brown color.Add 3mLof starch TS,and complete the titration.Perform a blank determination,and note the difference in volumes required.If the volume required for the specimen is less than 0.8of that required for the blank,repeat the procedure with a smaller specimen.The difference in volume corresponds to not more than 0.20mLof 0.1Nsodium thiosulfate for each g of Concentrate taken.
Acid value—
Dilute about 15g,accurately weighed,with 50mLof water,and titrate with 0.02Npotassium hydroxide VSto a phenolphthalein endpoint.Perform a blank determination,and make any necessary correction.Calculate the acid value taken by the formula:
56.11(AN/W),
in which Ais the number of mLof potassium hydroxide VSconsumed and Nis its normality,and Wis the weight,in g,of Concentrate taken.The limit is 0.5,calculated on the anhydrous basis.
Methyl ethyl ketone—
Internal standard solution—
Prepare a solution in water containing about 1mg per mLof methyl isobutyl ketone.
Standard preparation—
Prepare a solution in water containing an accurately known concentration of methyl ethyl ketone equivalent to about 1mg per mL.Pipet 5mLof this solution into a 100-mLvolumetric flask,add 5.0mLof Internal standard solution,add water to volume,and mix.
Test preparation—
Pipet 5mLof Internal standard solutioninto a 100-mLvolumetric flask,add Concentrate to volume,and mix.
Support—
Place about 90g of unsilanized support S1Ain a crystallizing dish,and cover it with chloroform.Stir the mixture thoroughly,and carefully remove the supernatant chloroform with an aspirator.Spread the moist support on a clean surface,and allow it to air-dry.Place the dried support in the crystallizing dish,and cover it with 0.5Nalcoholic potassium hydroxide TS.Allow it to stand for one-half hour with occasional stirring.Carefully pour off the supernatant alcoholic potassium hydroxide solution,and wash the moist support with water until the washing is neutral to phenolphthalein indicator.Spread the moist support on a clean surface,and allow it to air-dry.
Chromatographic system—
The gas chromatograph is equipped with a flame-ionization detector and a 0.6-m ×2-mm column packed with 25%liquid phase G16on unsilanized acid-and base-washed Supportwhich has been washed with chloroform,and conditioned as directed (see Chromatography á621ñ).The column is maintained at 70,and nitrogen is used as the carrier gas at a flow rate of about 30mLper minute.In a suitable chromatogram,the relative standard deviation of five replicate injections is not more than 3.0%,and the resolution is not less than 2.0.
,and nitrogen is used as the carrier gas at a flow rate of about 30mLper minute.In a suitable chromatogram,the relative standard deviation of five replicate injections is not more than 3.0%,and the resolution is not less than 2.0.
Procedure—
Inject about 3µLof the Standard preparationinto the gas chromatograph,record the chromatogram,and measure the peak response of each component.[NOTE—Clean the syringe after each injection with pentane.Do not use acetone.]Similarly inject about 3µLof the Test preparation,record the chromatogram,and measure the peak response of each component.Calculate the quantity,in mg,of methyl ethyl ketone in each mLof the Concentrate taken by the formula:
(1/0.95)C(RU/RS),
in which Cis the concentration,in mg per mL,of methyl ethyl ketone in the Standard preparation,and RUand RSare the ratios of the response of the methyl ethyl ketone to the response of the internal standard obtained from the Test preparationand the Standard preparation,respectively.The limit is 0.05mg per mL.
Assay—
Internal standard solution—
Dissolve a suitable quantity of triethylene glycol in water to obtain a solution containing about 15mg per mL.
Standard solution—
Prepare a solution of USP Isosorbide RSin water containing an accurately known concentration equivalent to about 25mg of C6H10O4per mL.
Standard preparations—
Pipet 2-,3-,4-,and 5-mLquantities of Standard solutioninto separate 50-mLvolumetric flasks,add 5.0mLof Internal standard solutionto each,add water to volume,and mix.
Assay preparation—
Transfer about 200mg of Concentrate,accurately weighed,to a 100-mLvolumetric flask,add 10.0mLof Internal standard solution,add water to volume,and mix.
Chromatographic system—
The gas chromatograph is equipped with a flame-ionization detector and a 3-mm ×0.6-m glass column packed with support S9.The column is maintained at 230,and nitrogen is used as the carrier gas.The retention time of the isosorbide peak is about 1.5,relative to that of triethylene glycol.
,and nitrogen is used as the carrier gas.The retention time of the isosorbide peak is about 1.5,relative to that of triethylene glycol.
System suitabilityand standard curve—
Inject 1-µLportions of each Standard preparation,and record each peak response.Plot the ratio of the peak response of isosorbide to that of triethylene glycol versus the concentration,in mg per mL,of isosorbide in the respective Standard preparation.The analytical system is suitable for conducting the assay if the correlation coefficient for the Standard curve is greater than 0.980,the resolution,R,is not less than 1.5,and neither tailing factor exceeds 2.0.
Procedure—
Inject a 1-µLportion of the Assay preparation,record the peak responses for the two major peaks,calculate the ratio of the peak responses,and determine the concentration,C,in mg per mL,of isosorbide in the Assay preparationby reference to the Standard curve.Calculate the quantity,in mg,of C6H10O4in the Concentrate taken by the formula:
100C.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1084
Pharmacopeial Forum:Volume No.28(3)Page 766
Phone Number:1-301-816-8305