Theophylline Capsules »Theophylline Capsules contain not less than 90.0percent and not more than 110.0percent of the labeled amount of anhydrous theophylline (C7H8N4O2). Packaging and storage— Preserve in well-closed containers. USP Reference standards á11ñ USP Theophylline RS. Identification— A: The contents of the Capsules respond to Identificationtests Aand Bunder Theophylline Tablets. 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. Dissolution á711ñ Medium: water;900mL. Apparatus 2: 50rpm. Time: 60minutes. Procedure— Determine the amount of C7H8N4O2dissolved from UVabsorbances at the wavelength of maximum absorbance at about 268nm of filtered portions of the solution under test,suitably diluted with 0.1Nhydrochloric acid,if necessary,in comparison with a Standard solution having a known concentration of USP Theophylline RSin the same medium. Tolerances— Not less than 80%(Q)of the labeled amount of C7H8N4O2is dissolved in 60minutes. Uniformity of dosage units á905ñ: meet the requirements. Assay— Mobile phase— Prepare a solution containing a mixture of water,methanol,and glacial acetic acid (64:35:1). Standard preparation— Dissolve an accurately weighed quantity of USP Theophylline RSin methanol to obtain a solution having a known concentration of about 400µg per mL. Assay preparation for hard Capsules— Remove,as completely as possible,the contents of not less than 20Capsules,weigh,and mix.Transfer an accurately weighed portion of the powder,equivalent to about 100mg of anhydrous theophylline,to a 250-mLvolumetric flask,add about 150mLof methanol,and shake to dissolve.Dilute with methanol to volume,mix,and filter,using a membrane filter. Assay preparation for soft Capsules— Cut open 20Capsules,and place them in a 200-mLvolumetric flask.Add 50mLof 6Nammonium hydroxide,shake to dissolve the contents,add water to volume,mix,and filter,discarding the first 20mLof the filtrate.Transfer an accurately measured portion of the filtrate,equivalent to about 100mg of anhydrous theophylline,to a 250-mLvolumetric flask,add methanol to volume,mix,and filter through a membrane filter. Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4-mm ×30-cm column that contains packing L1.The flow rate is about 2mLper minute.Chromatograph three replicate injections of the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation is not more than 2%. Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses.Calculate the quantity,in mg,of anhydrous theophylline in the portion of Capsule contents taken by the formula: 0.25C(rU/rS), in which Cis the concentration,in µg per mL,of USP Theophylline RSin the Standard preparation,and rUand rSare the peak responses obtained from 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 1896 Phone Number:1-301-816-8379