Theophylline and Guaifenesin Oral Solution »Theophylline and Guaifenesin Oral Solution contains not less than 90.0percent and not more than 110.0percent of the labeled amount of anhydrous theophylline (C7H8N4O2)and not less than 86.7percent and not more than 113.3percent of the labeled amount of guaifenesin (C10H14O4). Packaging and storage— Preserve in tight containers. USP Reference standards á11ñ USP Guaifenesin RS.USP Theophylline RS. Identification— Transfer a volume of Oral Solution,equivalent to about 150mg of theophylline,to a separator,add 15mLof water,and proceed as directed in the Identificationtest under Theophylline and Guaifenesin Capsules,beginning with “To a second separator.” Alcohol content (if present),Method IIá611ñ: between 90.0%and 110.0%of the labeled amount of C2H5OH,determined by the gas-liquid chromatographic procedure,acetone being used as the internal standard. Assay— pH6.5buffer solution and Mobile phase—Prepare as directed in the Assayunder Theophylline and Guaifenesin Capsules. Caffeine solution— Dissolve about 400mg of caffeine in 1000mLof a mixture of methanol and water (90:10),and mix. Standard preparation— Dissolve an accurately weighed quantity of USP Theophylline RSin pH6.5buffer solution,and dilute quantitatively with pH6.5buffer solutionto obtain a solution (Solution T)having a known concentration of about 900Jµg per mL,in which Jis the ratio of the labeled amount of theophylline to that of guaifenesin.Transfer about 90mg of USP Guaifenesin RS,accurately weighed,to a 200-mLvolumetric flask,add about 150mLof pH6.5buffer solution,shake to dissolve,dilute with pH6.5buffer solutionto volume,and mix.Pipet 10mLof this solution and 5mLof Solution Tinto a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix to obtain a Standard preparationhaving known concentrations of about 90µg of guaifenesin and about 90Jµg of theophylline per mL. Assay preparation— Transfer an accurately measured volume of Oral Solution,equivalent to about 90mg of guaifenesin,to a 200-mLvolumetric flask,dilute with pH6.5buffer solutionto volume,and mix.Transfer 10.0mLof this solution to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix. Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1.0mLper minute.Chromatograph a mixture of 4mLof Standard preparationand 1mLof Caffeine solution,and record the peak responses as directed for Procedure:the resolution,R,between the theophylline and caffeine peaks is not less than 3.0,and the relative standard deviation for replicate injections is not more than 2.0for theophylline and not more than 2.5%for guaifenesin. Procedure— Proceed as directed in the Assayunder Theophylline and Guaifenesin Capsules.Calculate the quantities,in mg,of anhydrous theophylline (C7H8N4O2)and guaifenesin (C10H14O4)per mLof the Oral Solution taken by the formula: (C/V)(rU/rS), in which Cis the concentration,in µg per mL,of the appropriate USP Reference Standard in the Standard preparation,Vis the volume,in mL,of Oral Solution taken,and rUand rSare the peak responses of the corresponding analyte in the Assay preparationand the Standard preparation,respectively. Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist Expert Committee:(PA1)Pharmaceutical Analysis 1 USP28–NF23Page 1902 Phone Number:1-301-816-8379