Mannitol
;)
D-Mannitol.
D-Mannitol [69-65-8].
»Mannitol contains not less than 96.0percent and not more than 101.5percent of C6H14O6,calculated on the dried basis.The amounts of total sugars,other polyhydric alcohols,and any hexitol anhydrides,if detected,are not included in the requirements nor the calculated amount under Other Impurities.
Packaging and storage—
Preserve in well-closed containers.
Identification,
Infrared Absorption á197Kñ.
Specific rotation á781Sñ:
between +137
and +145.
and +145.
Test solution—
Transfer about 1g of Mannitol,accurately weighed,to a 100-mLvolumetric flask,and add 40mLof ammonium molybdate solution (1in 10),which previously had been filtered if necessary.Add 20mLof 1Nsulfuric acid,dilute with water to volume,and mix.
Acidity—
Dissolve 5.0g in 50mLof carbon dioxide-free water,add 3drops of phenolphthalein TS,and titrate with 0.020Nsodium hydroxide to a distinct pink endpoint:not more than 0.30mLof 0.020Nsodium hydroxide is required for neutralization.
Loss on drying á731ñ—
Dry it at 105for 4hours:it loses not more than 0.3%of its weight.
for 4hours:it loses not more than 0.3%of its weight.
Chloride á221ñ—
A2.0-g portion shows no more chloride than corresponds to 0.20mLof 0.020Nhydrochloric acid (0.007%).
Sulfate á221ñ—
A2.0-g portion shows no more sulfate than corresponds to 0.20mLof 0.020Nsulfuric acid (0.01%).
Arsenic,Method IIá211ñ:
1ppm.
Reducing sugars—
To 5mLof alkaline cupric citrate TSadd 1mLof a saturated solution of Mannitol (about 200mg).Heat for 5minutes in a boiling water bath:not more than a very slight precipitate is formed.The amount determined in this test is not included in the calculated amount under Other Impurities.
Assay—
Mobile phase—
Use degassed water.
Resolution solution—
Dissolve sorbitol and USP Mannitol RSin water to obtain a solution having concentrations of about 4.8mg per mLof each.
Standard preparation—
Dissolve an accurately weighed quantity of USP Mannitol RSin water,and dilute quantitatively with water to obtain a solution having a known concentration of about 4.8mg per mL.
Assay preparation—
Transfer about 0.24g of Mannitol,accurately weighed,to a 50-mLvolumetric flask,dissolve in 10mLof water,dilute with water to volume,and mix.
Chromatographic system
(see Chromatography á621ñ)—The liquid chromatograph is equipped with a refractive index detector that is maintained at a constant temperature and a 4-mm ×25-cm column that contains packing L19.The column temperature is maintained at a temperature between 30and 85controlled within ±2of the selected temperature,and the flow rate is about 0.5mLper 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%.In a similar manner,chromatograph the Resolution solution:the resolution,R,between the sorbitol and mannitol peaks is not less than 2.0.
and 85controlled within ±2of the selected temperature,and the flow rate is about 0.5mLper 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%.In a similar manner,chromatograph the Resolution solution:the resolution,R,between the sorbitol and mannitol peaks is not less than 2.0.
Procedure—
Separately inject equal volumes (about 20µL)of the Assay preparationand the Standard preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C6H14O6,in the Mannitol taken by the formula:
50C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Mannitol RSin the Standard preparation;and rUand rSare the peak responses 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 1183
Pharmacopeial Forum:Volume No.27(5)Page 3017
Phone Number:1-301-816-8305