»Guaifenesin contains not less than 98.0percent and not more than 102.0percent of C10H14O4,calculated on the dried basis.
Packaging and storage Preserve in tight containers.
A:Infrared Absorption á197Kñ.
B:Ultraviolet Absorption á197Uñ
Solution: 40µg per mL.
C: Mix about 5mg with 1drop of formaldehyde and a few drops of sulfuric acid:a deep cherry red to purple color is produced.
Melting range á741ñ: between 78and 82,but the range between beginning and end of melting does not exceed 3.
Loss on drying á731ñ Dry it in vacuum,but at a pressure not below 10mm of mercury,at 60to constant weight:it loses not more than 0.5%of its weight.
Heavy metals,Method Iá231ñ The limit is 0.0025%.
Solution A,Solution B,andMobile phase Proceed as directed in the Assay.
Chromatographic system Proceed as directed in the Assay.To evaluate the system suitability requirements,use the Resolution solutionand the Standard preparationprepared as directed in the Assay.
Test solution Dissolve about 20mg of Guaifenesin in 10mLof Solution B.
Diluted test solution Transfer 1.0mLof the Test solutionto a 100-mLvolumetric flask,dilute with Solution Bto volume,and mix.
Procedure Separately inject equal volumes (about 10µL)of the Test solutionand the Diluted test solutioninto the chromatograph,record the chromatograms,and measure the areas for the major peaks.All of the peaks are baseline resolved.Calculate the percentage of each impurity in the portion of Guaifenesin taken by the formula:
F(ri/rS),in which Fis a response factor equal to 0.63for the guaiacol peak,having a relative retention time of 1.4,and 1.0for all other impurities;riis the area of each peak,other than that of the main guaifenesin peak,obtained from the Test solution;and rSis the area of the main peak obtained from the Diluted test solution:not more than 1.5%of 2-(2-methoxyphenoxy)-1,3-propanediol (guaifenesin b-isomer),the peak for which occurs at a relative retention time of about 0.9,is found;not more than 0.03%of guaiacol is found;not more than 0.5%of any other individual impurity is found;and not more than 1.0%of total impurities,excluding guaifenesin b-isomer and guaiacol,is found.
Organic volatile impurities,Method IVá467ñ: meets the requirements.
Solution A Prepare a mixture of water and glacial acetic acid (990:10).
Solution B Use acetonitrile.
Mobile phase Use variable mixtures of Solution Aand Solution Bas directed for Chromatographic system.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Resolution solution Prepare a solution in Solution Bcontaining about 0.5mg of USP Guaifenesin RSand 0.02mg of USP Guaiacol RSin each mL.
Standard preparation Prepare a solution of USP Guaifenesin RSin Solution Bhaving a known concentration of about 0.5mg per mL.
Assay preparation Transfer about 25mg of Guaifenesin,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with Solution Bto volume,and mix.
Chromatographic system (see Chromatography á621ñ) The liquid chromatograph is equipped with a 276-nm detector and a 4.6-mm ×25-cm column that contains 5-µm packing L1.The flow rate is about 1mLper minute.The chromatograph is programmed as follows.
Procedure Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the peak responses.Calculate the quantity of C10H14O4in the portion of Guaifenesin taken by the formula:
50C(rU/rS),in which Cis the concentration,in mg per mL,of USP Guaifenesin RSin the Standard preparation;and rUand rSare the peak areas obtained from the Assay preparationand the Standard preparation,respectively.Calculate the percentage of C10H14O4in the portion of Guaifenesin taken.To this value,add the percentage of guaifenesin b-isomer found in the test for Chromatographic purity.
Auxiliary Information Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28NF23Page 922Pharmacopeial Forum:Volume No.27(4)Page 2735