Loperamide Hydrochloride Oral Solution
»Loperamide Hydrochloride Oral Solution contains not less than 90.0percent and not more than 110.0percent of the labeled amount of loperamide hydrochloride (C29H33ClN2O2·HCl).
Packaging and storage— Preserve in tight,light-resistant containers.Store below 40,preferably between 15and 30,unless otherwise specified by the manufacturer.
Identification—
A: Infrared Absorption á197Kñ—
Test specimen— Transfer a volume of Oral Solution,equivalent to about 24mg of loperamide hydrochloride,to a separator containing about 100mLof water and 1mLof sodium hydroxide solution (1in 2),and gently swirl the contents.Add 50mLof methylene chloride,shake gently by hand,releasing pressure often,and then shake by mechanical means for 20minutes.Allow the layers to separate.Transfer the lower methylene chloride layer to a separator containing 100mLof water.Shake gently by hand,releasing pressure often,and then shake by mechanical means for 10minutes.Allow the layers to separate.Transfer the lower methylene chloride layer to a 250-mLbeaker,and evaporate on a steam bath with the aid of a current of air to dryness.Add 10mLof methanol and 500mg of potassium bromide to the beaker,and mix.Evaporate on a steam bath with the aid of a current of air to dryness,and use the residue.
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.
Uniformity of dosage units á905ñ—
FOR ORAL SOLUTION PACKAGED IN SINGLE-UNIT CONTAINERS: meets the requirements.
Deliverable volume á698ñ—
FOR ORAL SOLUTION PACKAGED IN MULTIPLE-UNIT CONTAINERS: meets the requirements.
pHá791ñ: between 2.7and 6.5.
Alcohol content,Method IIá611ñ(if present): between 90.0%and 110.0%of the labeled amount of C2H5OHis found.
Assay—
Buffer solution— Transfer 3.0g of monobasic potassium phosphate to a 1-Lvolumetric flask,dissolve in and dilute with water to volume,and mix.
Mobile phase— Prepare a mixture of Buffer solutionand acetonitrile (63:37),and adjust with 0.9Mphosphoric acid to a pHof 3.0.Mix,filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Loperamide Hydrochloride RSin methanol,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a known concentration of about 10µg per mL.
Assay preparation— Transfer an accurately measured volume of Oral Solution,equivalent to about 1.0mg of loperamide hydrochloride,to a 100-mLvolumetric flask.Dilute with Mobile phaseto volume,mix,and filter.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 214-nm detector and a 4.0-mm ×8.0-cm column that contains 5-µm packing L7.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparation,and record the peak areas as directed for Procedure:the tailing factor is not more than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10µL)of the Standard preparation and the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity,in mg,of loperamide hydrochloride (C29H33ClN2O2·HCl)in each mLof Oral Solution taken by the formula:
100(C/V)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Loperamide Hydrochloride RSin the Standard preparation;Vis the volume of Oral Solution taken to prepare the Assay preparation;and rUand rSare the peak areas obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28–NF23Page 1146
Pharmacopeial Forum:Volume No.29(6)Page 1918
Phone Number:1-301-816-8251