Theophylline Oral Solution
»Theophylline Oral Solution contains not less than 95.0percent and not more than 105.0percent of theophylline (C7H8N4O2).
Packaging and storage— Preserve in tight,light-resistant containers,and avoid exposure to excessive heat.
Labeling— Label it to indicate the alcohol content (if present).
Identification—
A: Thin-Layer Chromatographic Identification Test á201ñ—
Test solution— Transfer a portion of Oral Solution,equivalent to about 100mg of theophylline,to a separatory funnel.Extract with two 25-mLportions of chloroform,collecting the extracts in a 100-mLvolumetric flask.Dilute with methanol to volume,and mix.
Standard solution— Prepare a solution of USP Theophylline RSin methanol containing about 1mg per mL.
Application volume: 20µL.
Developing solvent system: a mixture of chloroform,methanol,and acetic acid (89:10:1).
Procedure— Apply the Standard solutionand the Test solutionas directed in the chapter,and dry the plate in a current of cool air.Place the plate in a suitable chromatographic chamber lined with filter paper and previously equilibrated with the Developing solvent system.Upon removing the plate from the chamber,dry with a current of warm air in a suitable hood.
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.
Microbial limits á61ñ— It meets the requirements of the tests for absence of Salmonellaspecies and Escherichia coli.The total aerobic microbial count does not exceed 100cfu per mL,and the total combined molds and yeasts count does not exceed 50cfu per mL.
pHá791ñ: between 4.3and 4.7.
Alcohol content,Method IIá611ñ(if present): between 90.0%and 115.0%of the labeled amount of C2H5OHis found,using acetone as the internal standard.
Assay—
Mobile phase— Prepare a filtered and degassed mixture of water,methanol,and acetic acid (76.5:22.5:1)containing 200mg of sodium 1-octanesulfonate in each 1000mLof solution.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
System suitability preparation— Dissolve accurately weighed quantities of USP Theophylline RSand caffeine in water to obtain a solution containing about 0.68mg of each per mL.
Standard preparation— Dissolve an accurately weighed quantity of USP Theophylline RSin water to obtain a solution having a known concentration of about 0.68mg per mL.
Assay preparation— Transfer an accurately measured volume of Oral Solution,equivalent to about 68mg of theophylline,to a 100-mLvolumetric flask.Dilute with water to volume,and mix.
Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 4.0-mm ×30-cm column that contains packing L1.The flow rate is about 2.0mLper minute.Chromatograph the System suitability preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.6for theophylline and 1.0for caffeine;the resolution,R,between theophylline and caffeine is not less than 2.0;the tailing factor is not more than 2;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of theophylline (C7H8N4O2)in the portion of Oral Solution taken by the formula:
100C(rU/rS),
in which Cis the concentration,in mg 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 1898
Pharmacopeial Forum:Volume No.27(5)Page 3044
Phone Number:1-301-816-8379