Sorbitol
;)
D-Glucitol.
D-Glucitol [50-70-4].
»Sorbitol contains not less than 91.0percent and not more than 100.5percent of D-sorbitol,calculated on the anhydrous basis.The amounts of total sugars,other polyhydric alcohols,and any hexitol anhydrides,if detected,are not included in the requirements,nor in the calculated amount under Other Impurities.
Packaging and storage—
Preserve in well-closed containers.Store at room temperature.
Labeling—
Sorbitol intended for use in preparing parenteral dosage forms is so labeled.
Identification—
A:
Dissolve 1g of Sorbitol in 75mLof water.Transfer 3mLof this solution to a 15-cm test tube,add 3mLof freshly prepared catechol solution (1in 10),and mix.Add 6mLof sulfuric acid,mix again,then gently heat the tube in a flame for about 30seconds:a deep pink or wine red color appears.
B:
The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
Microbial limits á61ñ—
The total aerobic count using the Plate Methodis not more than 1000cfu per g and the total combined molds and yeasts count is not more than 100cfu per g.
pHá791ñ:
between 3.5and 7.0,in a 10%(w/w)solution in carbon dioxide–free water.
Water,Method Iá921ñ:
not more than 1.5%.
Residue on ignition á281ñ:
not more than 0.1%,determined on a 1.5-g portion,accurately weighed.
Reducing sugars—
Dissolve 3.3g of Sorbitol in 3mLof water with the aid of gentle heat.Cool,and add 20.0mLof cupric citrate TSand a few glass beads.Heat so that boiling begins after 4minutes,and maintain boiling for 3minutes.Cool rapidly,and add 40mLof diluted acetic acid,60mLof water,and 20.0mLof 0.05Niodine VS.With continuous shaking,add 25mLof a mixture of 6mLof hydrochloric acid and 94mLof water.When the precipitate has dissolved,titrate the excess of iodine with 0.05Nsodium thiosulfate VSusing 2mLof starch TS,added towards the end of the titration,as an indicator.Not less than 12.8mLof 0.05Nsodium thiosulfate VSis required,corresponding to not more than 0.3%of reducing sugars,as glucose.The amount determined in this test is not included in the calculated amount under Other Impurities.
Limit of nickel—
Test solution—
Dissolve 20.0g of Sorbitol in diluted acetic acid,and dilute with diluted acetic acid to 150mL.Add 2.0mLof a saturated ammonium pyrrolidinedithiocarbamate solution (containing about 10g of ammonium pyrrolidinedithiocarbamate per L)and 10.0mLof methyl isobutyl ketone,and shake for 30seconds.Protect from bright light.Allow the two layers to separate,and use the methyl isobutyl ketone layer.
Blank solution—
Prepare as directed for Test solution,except to omit the use of Sorbitol.
Standard solutions—
Prepare as directed for Test solution,except to prepare three solutions by adding 0.5mL,1.0mL,and 1.5mLof nickel standard solution TS.
Procedure—
Set the instrument to zero using the Blank solution.Concomitantly determine the absorbances of the Standard solutions and the Test solution at least three times each,at the wavelength of maximum absorbance at 232.0nm,with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering á851ñ)equipped with a nickel hollow-cathode lamp and an air–acetylene flame.Record the average of the steady readings for each of the Standard solutions and the Test solution.Between each measurement,aspirate the Blank solution,and ascertain that the reading returns to zero.Plot the absorbances of the Standard solutions and the Test solution versus the added quantity of nickel.Extrapolate the line joining the points on the graph until it meets the concentration axis.The distance between this point and the intersection of the axes represents the concentration of nickel in the Test solution.Not more than 1µg per g is found.
Other requirements—
If labeled for use in preparing parenteral dosage forms,it also meets the following requirements.
Clarityand color of solution—
Dissolve a 10.0-g portion in carbon dioxide–free water,and dilute with carbon dioxide-free water to 100.0mL:the solution is clear and colorless.
Bacterial endotoxins á85ñ:
not more than 4USP Endotoxin Units per g for parenteral dosage forms having a concentration of less than 100g of sorbitol per Land not more than 2.5USP Endotoxin Units per g for parenteral dosage forms having a concentration of 100g or more of sorbitol per L.
Chloride á221ñ—
A1.5-g portion shows no more chloride than corresponds to 0.10mLof 0.020Nhydrochloric acid.Not more than 0.0050%is found.
Sulfate á221ñ—
A1.0-g portion shows no more sulfate than corresponds to 0.10mLof 0.020Nsulfuric acid.Not more than 0.01%is found.
Assay—
Mobile phase—
Use degassed water.
Resolution solution—
Dissolve mannitol and USP Sorbitol RSin water to obtain a solution having concentrations of about 4.8mg per g of each.
Standard preparation—
Dissolve an accurately weighed quantity of USP Sorbitol RSin water to obtain a solution having a known concentration of about 4.8mg per g.
Assay preparation—
Dissolve about 0.10g of Sorbitol,accurately weighed,in water,and dilute with water to about 20g.Accurately record the final solution weight,and mix thoroughly.
Chromatographic system(see Chromatography á621ñ)—
The liquid chromatograph is equipped with a refractive index detector that is maintained at a constant temperature of about 35
and a 7.8-mm ×10-cm column that contains packing L34.The column temperature is maintained at a constant temperature of about 50,controlled within ±2,and the flow rate is about 0.7mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.6for mannitol and 1.0for sorbitol;and the resolution,R,between sorbitol and mannitol is not less than 2.0.
and a 7.8-mm ×10-cm column that contains packing L34.The column temperature is maintained at a constant temperature of about 50,controlled within ±2,and the flow rate is about 0.7mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.6for mannitol and 1.0for sorbitol;and the resolution,R,between sorbitol and mannitol is not less than 2.0.
Procedure—
Separately inject equal volumes (about 10µL)of the Assay preparationand the Standard preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the percentage,on the anhydrous basis,of D-sorbitol in the portion of Sorbitol taken by the formula:
[10,000(CS/CU)(rU/rS)]/(100–W),
in which CSis the concentration,in mg per g,of USP Sorbitol RSin the Standard preparation;CUis the concentration,in mg per g,of Sorbitol in the Assay preparation;rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively;and Wis the percentage obtained in the test for Water.
Auxiliary Information—
Staff Liaison:Catherine Sheehan,B.Sc.,Scientist
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 3085
Pharmacopeial Forum:Volume No.30(3)Page 992
Phone Number:1-301-816-8262