Theophylline Oral Solution
» Theophylline Oral Solution contains not less than 95.0 percent and not more than 105.0 percent 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).
USP Reference standards 11
A: Thin-Layer Chromatographic Identification Test 201
Test solution Transfer a portion of Oral Solution, equivalent to about 100 mg of theophylline, to a separatory funnel. Extract with two 25-mL portions of chloroform, collecting the extracts in a 100-mL volumetric flask. Dilute with methanol to volume, and mix.
Standard solution Prepare a solution of USP Theophylline RS in methanol containing about 1 mg per mL.
Application volume: 20 µL.
Developing solvent system: a mixture of chloroform, methanol, and acetic acid (89:10:1).
Procedure Apply the Standard solution and the Test solution as 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 preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Microbial enumeration tests 61 and Tests for specified microorganisms 62 It meets the requirements of the tests for absence of Salmonella species and Escherichia coli. The total aerobic microbial count does not exceed 100 cfu per mL, and the total combined molds and yeasts count does not exceed 50 cfu per mL.
pH 791: between 4.3 and 4.7.
Alcohol content, Method II 611 (if present): between 90.0% and 115.0% of the labeled amount of C2H5OH is found, using acetone as the internal standard.
Mobile phase Prepare a filtered and degassed mixture of water, methanol, and acetic acid (76.5:22.5:1) containing 200 mg of sodium 1-octanesulfonate in each 1000 mL of solution. Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability preparation Dissolve accurately weighed quantities of USP Theophylline RS and caffeine in water to obtain a solution containing about 0.68 mg of each per mL.
Standard preparation Dissolve an accurately weighed quantity of USP Theophylline RS in water to obtain a solution having a known concentration of about 0.68 mg per mL.
Assay preparation Transfer an accurately measured volume of Oral Solution, equivalent to about 68 mg of theophylline, to a 100-mL volumetric flask. Dilute with water to volume, and mix.
Chromatographic system (see Chromatography 621) 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 2.0 mL per minute. Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.6 for theophylline and 1.0 for 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 10 µL) of the Standard preparation and the Assay preparation into 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 C is the concentration, in mg per mL, of USP Theophylline RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 4826Pharmacopeial Forum: Volume No. 27(5) Page 3044