Identification—
A:
Thin-Layer Chromatographic Identification Test á201ñ—
Test solution—
Transfer a volume of Oral Solution,equivalent to about 10mg of codeine phosphate,to a separator,and add 5mLof water,5mLof methylene chloride,and 1mLof ammonium hydroxide.Shake for 1minute,allow the layers to separate,and use the clear,lower layer.
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 preparationcorrespond to those 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,
Escherichia coli,Staphylococcus aureus,and
Pseudomonas aeruginosa.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.
Assay—
Diluent—
Prepare a mixture of methanol and water (80:20).
Mobile phase—
Prepare a filtered and degassed mixture of methanol,water,0.1Nammonium hydroxide solution,and 0.1Nammonium nitrate solution (27:3:2:1).Make adjustments if necessary (see
System Suitabilityunder
Chromatography á621ñ).
Assay preparation—
Using a pipet calibrated “to contain”,transfer an accurately measured volume of Oral Solution,equivalent to about 10mg of bromodiphenhydramine hydrochloride and 8mg of codeine phosphate,to a 100-mLvolumetric flask,dissolve in and dilute with Diluentto volume,and mix.
Chromatographic system (see Chromatography á621ñ)—
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 1.0mLper minute.Chromatograph the
Standard preparation,and record the peak responses as directed for
Procedure:the relative retention times are about 1.0for bromodiphenhydramine and 1.4for 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 20µL)of the
Standard preparationand the
Assay preparationinto the chromatograph,record the chromatograms,and measure the peak responses for bromodiphenhydramine and codeine.Calculate the quantity,in mg,of bromodiphenhydramine hydrochloride (C
17H
20BrNO·HCl)in each mLof the Oral Solution taken by the formula:
100(C/V)(rU/rS),
in which
Cis the concentration,in mg per mL,of
USP Bromodiphenhydramine Hydrochloride RSin the
Standard preparation;Vis the volume,in mL,of Oral Solution taken to prepare the
Assay preparation;and
rUand
rSare the bromodiphenhydramine peak responses obtained from the
Assay preparationand the
Standard preparation,respectively.Calculate the quantity,in mg,of codeine phosphate hemihydrate (C
18H
21NO
3·H
3PO
4·½H
2O)in each mLof the Oral Solution taken by the formula:
(406.37/397.36)(100C/V)(rU/rS),
in which 406.37and 397.36are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate,respectively;
Cis the concentration,in mg per mL,of
USP Codeine Phosphate RSin the
Standard preparation;Vis the volume,in mL,of Oral Solution taken to prepare the
Assay preparation;and
rUand
rSare the codeine peak responses obtained from the
Assay preparationand the
Standard preparation,respectively.