Cromolyn Sodium
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4H-1-Benzopyran-2-carboxylic acid,5,5¢-[(2-hydroxy-1,3-propanediyl)bis(oxy)bis[4-oxo-,disodium salt].
Disodium 5,5¢-[(2-hydroxytrimethylene)dioxy]bis[4-oxo-4H-1-benzopyran-2-carboxylate] [15826-37-6].
»Cromolyn Sodium contains not less than 98.0percent and not more than 101.0percent of C23H14Na2O11,calculated on the anhydrous basis.
Packaging and storage—
Preserve in tight containers.
Identification—
A:
The IRabsorption spectrum of a potassium bromide dispersion of it,previously dried in vacuum at 105
to constant weight,exhibits maxima only at the same wavelengths as that of a similar preparation of USP Cromolyn Sodium RS.
to constant weight,exhibits maxima only at the same wavelengths as that of a similar preparation of USP Cromolyn Sodium RS.
B:
The UVabsorption spectrum of a 1in 40,000solution in pH7.4sodium phosphate bufferprepared as directed in the Assayexhibits maxima at the same wavelengths as that of a similar solution of USP Cromolyn Sodium RS,concomitantly measured.
Acidity or alkalinity—
Dissolve 1.0g in 25mLof carbon dioxide-free water,and add two drops of bromothymol blue TS.If the solution is yellow,not more than 0.25mLof 0.1Nsodium hydroxide is required to produce a blue color.If the solution is blue,not more than 0.25mLof 0.1Nhydrochloric acid is required to produce a yellow color.
Water,Method Iá921ñ:
not more than 10.0%.
Heavy metals,Method IIá231ñ:
0.002%.
Limit of oxalate—
Dissolve 100mg in 20mLof water,add 5.0mLof iron salicylate TS,and dilute with water to 50mL.Determine the absorbance of the solution at 480nm against a water blank.The absorbance is not less than that of a solution containing 350µg of oxalic acid prepared in the same manner (0.35%).
Related compounds—
Dissolve 100mg of Cromolyn Sodium in 10.0mLof a mixture of water,stabilizer-free tetrahydrofuran,and acetone (6:4:1).Similarly prepare a solution of USP Cromolyn Sodium RSin the same solvent mixture having a concentration of 10mg per mL(Standard solution A).Quantitatively dilute a volume of Standard solution Awith the same solvent mixture to obtain a diluted standard solution having a concentration of 0.05mg per mL(Standard solution B).Apply 10-µLportions of the test solution,Standard solution A,and Standard solution Bto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of chloroform,methanol,and glacial acetic acid (9:9:2)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Locate the spots on the plate by viewing under short-wavelength UVlight:the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from Standard solution A.Any spot in the chromatogram obtained from the test solution moving ahead of the principal spot is not more intense than the spot in the chromatogram obtained from Standard solution B(0.5%).
Organic volatile impurities,Method Iá467ñ:
meets the requirements.
Assay—
pH7.4Sodium phosphate buffer—
Dissolve 70g of anhydrous dibasic sodium phosphate in 900mLof water.Adjust to a pHof 7.4by the addition of dilute phosphoric acid (1in 10).Dilute with water to 1000mL,and mix.Transfer 10mLof this solution to a 100-mLvolumetric flask,dilute with water to volume,and mix.
Standard preparation—
Dissolve an accurately weighed quantity of USP Cromolyn Sodium RSin water to obtain a solution having a known concentration of about 250µg per mL.Transfer 10mLof this solution to a 100-mLvolumetric flask,add 1mLof pH7.4Sodium phosphate buffer,dilute with water to volume,and mix.The final concentration is about 25µg per mL.
Assay preparation—
Transfer about 100mg of Cromolyn Sodium,accurately weighed,to a 1000-mLvolumetric flask,dissolve in about 100mLof water,dilute with water to volume,and mix.Pipet 25mLof this solution into a 100-mLvolumetric flask,add 1mLof pH7.4Sodium phosphate buffer,dilute with water to volume,and mix.
Procedure—
Concomitantly determine the absorbances of the Standard preparationand the Assay preparationin 1-cm cells at the wavelength of maximum absorbance at about 326nm,with a suitable spectrophotometer,using a 1in 100solution of pH7.4Sodium phosphate bufferas the blank.Calculate the quantity,in mg,of C23H14Na2O11in the Cromolyn Sodium taken by the formula:
4C(AU/AS),
in which Cis the concentration,in µg per mL,of USP Cromolyn Sodium RSin the Standard preparation;and AUand ASare the absorbances of the solutions from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Kahkashan Zaidi,Ph.D.,Senior Scientific Associate
Expert Committee:(AER)Aerosols
USP28–NF23Page 549
Phone Number:1-301-816-8269