Loperamide Hydrochloride
;)
1-Piperidinebutanamide,4-(4-chlorophenyl)-4-hydroxy-N,N-dimethyl-a,a-diphenyl-,monohydrochloride.
4-(p-Chlorophenyl)-4-hydroxy-N,N-dimethyl-a,a-diphenyl-1-piperidinebutyramide monohydrochloride [34552-83-5].
»Loperamide Hydrochloride contains not less than 98.0percent and not more than 102.0percent of C29H33ClN2O2·HCl,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Identification—
A:
Infrared Absorption á197Kñ.
B:
Transfer about 40mg,accurately weighed,to a 100-mLvolumetric flask,dissolve in about 50mLof isopropyl alcohol,add 10mLof 0.1Nhydrochloric acid,dilute with isopropyl alcohol to volume,and mix:the UVabsorption spectrum between 250and 300nm of this solution exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Loperamide Hydrochloride RS,concomitantly measured.
Loss on drying á731ñ—
Dry it in vacuum at 80
for 4hours:it loses not more than 0.5%of its weight.
for 4hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ:
not more than 0.2%.
Heavy metals,Method IIá231ñ:
0.002%.
Chromatographic purity—
Prepare a test solution in chloroform containing 10mg per mL.Apply 10µLof this solution and 10µLof a Standard solution of USP Loperamide Hydrochloride RSin chloroform containing 10mg per mLto a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of chloroform,methanol,and formic acid (85:10:5)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the plate to air-dry.Locate the spots on the plate by exposing it to fumes of iodine:the spot obtained from the test solution corresponds in RFvalue,color,and intensity to that obtained from the Standard solution,and no secondary spots are observed.
Chloride content—
Using about 13mg,accurately weighed,proceed as directed under Oxygen Flask Combustion á471ñ,using a mixture of 10mLof 0.02Nsodium hydroxide and 2drops of 30percent hydrogen peroxide as the absorbing liquid.When combustion is complete and the combustion gases absorbed,rinse the stopper,sample holder,and inner walls of the flask with 50mLof isopropyl alcohol.Add 4mLof 0.1Nnitric acid,and titrate with 0.01Nmercuric nitrate VS,using diphenylcarbazone TSas the indicator.Each mLof 0.01Nmercuric nitrate is equivalent to 0.3545mg of chlorine:between 13.52%and 14.20%is found.
Assay—
Neutralized acetic acid—
Dissolve 10mg of a-naphtholbenzein in 100mLof glacial acetic acid,and titrate with 0.1Nperchloric acid to a green endpoint,disregarding the amount of titrant consumed.
Procedure—
Dissolve about 375mg,accurately weighed,of Loperamide Hydrochloride in 25mLof Neutralized acetic acid.Add 10mLof mercuric acetate solution (prepared by dissolving 1g of mercuric acetate in 33mLof Neutralized acetic acid)and titrate with 0.1Nperchloric acid VSto the original green color of the Neutralized acetic acid.Each mLof 0.1Nperchloric acid is equivalent to 51.35mg of C29H33ClN2O2·HCl.
Auxiliary Information—
Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28–NF23Page 1145
Phone Number:1-301-816-8251