Bromodiphenhydramine Hydrochloride and Codeine Phosphate Oral Solution
» Bromodiphenhydramine Hydrochloride and Codeine Phosphate Oral Solution contains not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of bromodiphenhydramine hydrochloride (C17H20 BrNO·HCl) and codeine phosphate hemihydrate (C18H21NO3·H3PO4·½H2O).
Packaging and storage Preserve in tight, light-resistant containers.
Labeling Label it to indicate the alcohol content.
USP Reference standards 11
A: Thin-Layer Chromatographic Identification Test 201
Test solution Transfer a volume of Oral Solution, equivalent to about 10 mg of codeine phosphate, to a separator, and add 5 mL of water, 5 mL of methylene chloride, and 1 mL of ammonium hydroxide. Shake for 1 minute, allow the layers to separate, and use the clear, lower layer.
Standard solution Prepare a solution of USP Bromodiphenhydramine Hydrochloride RS and USP Codeine Phosphate RS in methanol containing 10 mg of each per mL.
Developing solvent system: a mixture of alcohol and ammonium hydroxide (49:1).
B: The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those 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, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. 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 4.5 and 6.5.
Alcohol content, Method II 611: between 4.0% and 6.0% is found.
Diluent Prepare a mixture of methanol and water (80:20).
Mobile phase Prepare a filtered and degassed mixture of methanol, water, 0.1 N ammonium hydroxide solution, and 0.1 N ammonium nitrate solution (27:3:2:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation Dissolve accurately weighed quantities of USP Bromodiphenhydramine Hydrochloride RS and USP Codeine Phosphate RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having known concentrations of about 100 µg per mL and 80 µg per mL, respectively.
Assay preparation Using a pipet calibrated to contain, transfer an accurately measured volume of Oral Solution, equivalent to about 10 mg of bromodiphenhydramine hydrochloride and 8 mg of codeine phosphate, to a 100-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30.0-cm column that contains packing L3. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for bromodiphenhydramine and 1.4 for codeine; the resolution, R, between bromodiphenhydramine and codeine is not less than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses for bromodiphenhydramine and codeine. Calculate the quantity, in mg, of bromodiphenhydramine hydrochloride (C17H20BrNO·HCl) in each mL of the Oral Solution taken by the formula:
100(C/V)(rU / rS)in which C is the concentration, in mg per mL, of USP Bromodiphenhydramine Hydrochloride RS in the Standard preparation; V is the volume, in mL, of Oral Solution taken to prepare the Assay preparation; and rU and rS are the bromodiphenhydramine peak responses obtained from the Assay preparation and the Standard preparation, respectively. Calculate the quantity, in mg, of codeine phosphate hemihydrate (C18H21NO3·H3PO4·½H2O) in each mL of the Oral Solution taken by the formula:
(406.37/397.36)(100C/V)(rU / rS)in which 406.37 and 397.36 are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate, respectively; C is the concentration, in mg per mL, of USP Codeine Phosphate RS in the Standard preparation; V is the volume, in mL, of Oral Solution taken to prepare the Assay preparation; and rU and rS are the codeine peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2391Pharmacopeial Forum: Volume No. 27(5) Page 2980