Propoxyphene Hydrochloride and Acetaminophen Tablets
»Propoxyphene Hydrochloride and Acetaminophen Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amounts of propoxyphene hydrochloride (C22H29NO2·HCl)and acetaminophen (C8H9NO2).
Packaging and storage— Preserve in tight containers.
Identification— Transfer 1finely ground Tablet to a test tube.If the Tablets are coated,first immerse the Tablet in acetone for 1½minutes,remove the shell,and grind.Add 5mLof methanol,shake for 5minutes,and centrifuge.Use the clear supernatant as the Test solution.Prepare a Standard solutionin methanol containing,in each mL,130mg of USP Acetaminophen RSand 13mg of USP Propoxyphene Hydrochloride RS.Apply 5µLof the Test solutionon a line parallel to and about 2cm from the bottom edge of a 20-×5-cm thin-layer chromatographic plate (see Chromatography á621ñ)coated with chromatographic silica gel mixture,and apply 5µLof the Standard solutionseparately on the starting line.Place the plate in a developing chamber containing a mixture of butyl acetate,chloroform,and formic acid (60:40:20),and develop the chromatogram until the solvent front has moved about 15cm above the line of application.Remove the plate,allow to dry in a hood,and view under short-wavelength UVlight:the RFvalue of the principal spot from the Test solutioncorresponds to that from the Standard solution.Spray the plate with iodoplatinate TS:the RFvalue of the orange-brown spot from the Test solutioncorresponds to that from the Standard solution.
Dissolution,Procedure for a Pooled Sample á711ñ—
Medium:pH4.5acetate buffer, prepared as directed in the test for Dissolutionunder Propoxyphene Hydrochloride,Aspirin and Caffeine Capsules;700mL.
Apparatus 2: 50rpm.
Time: 30minutes.
Procedure— Proceed as directed in the Assay,using a filtered portion of the solution under test,diluted with Mobile phase,and a Standard solution having accurately known concentrations of USP Propoxyphene Hydrochloride RSand USP Acetaminophen RSin Mobile phase.Calculate the amounts of propoxyphene hydrochloride (C22H29NO2·HCl)and acetaminophen (C8H9NO2)dissolved.
Tolerances— Not less than 80%(Q)of the labeled amount of C22H29NO2·HCl and not less than 80%(Q)of the labeled amount of C8H9NO2are dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements for Content Uniformitywith respect to propoxyphene hydrochloride.
Assay—
Mobile phase— Mix 0.15%diethylamine in water,adjusted with phosphoric acid to a pHof 3.2±0.2,and acetonitrile (4:1).Sonicate for 15minutes,and filter through a filter having a porosity of 0.5µm or finer.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation 1— Transfer about 2Jmg of USP Acetaminophen RS,accurately weighed,to a 10-mLvolumetric flask,Jbeing the ratio of the labeled amount,in mg,of acetaminophen to the labeled amount,in mg,of propoxyphene hydrochloride in each Tablet.Transfer about 2mg of USP Propoxyphene Hydrochloride RS,accurately weighed,to the same flask.Add about 5mLof Mobile phase,swirl to dissolve,dilute with Mobile phaseto volume,and mix.This solution contains about 0.2mg of USP Propoxyphene Hydrochloride RSand 0.2Jmg of USP Acetaminophen RSper mL.
Standard preparation 2— Transfer 5.0mLof Standard preparation 1to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.This solution contains about 0.01Jmg of USP Acetaminophen RSper mL.
Assay preparation 1— Weigh and finely powder not less than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 40mg of propoxyphene hydrochloride,to a 200-mLvolumetric flask,add about 150mLof Mobile phase,shake by mechanical means for 30minutes,sonicate for 5minutes,dilute with Mobile phaseto volume,mix,and filter,discarding the first 20mLof the filtrate.Use the clear filtrate as Assay preparation 1.
Assay preparation 2— Transfer 5.0mLof Assay preparation 1to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 210-nm detector and a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1mLper minute.Chromatograph Standard preparation 1,and record the responses as directed for Procedure:the tailing factor for the propoxyphene peak is not more than 2.0,and the relative standard deviation for replicate injections is not more than 2.0%.Chromatograph Standard preparation 2,and record the responses as directed for Procedure:the tailing factor for the acetaminophen peak is not more than 1.5,and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— [NOTE—Use peak areas where peak responses are indicated.]Separately inject equal volumes (about 20µL)of Standard preparation 1,Standard preparation 2,Assay preparation 1,and Assay preparation 2into the chromatograph,record the chromatograms using both the 210-nm and the 254-nm detectors,and measure the responses for the propoxyphene hydrochloride peaks obtained using the 210-nm detector and for the acetaminophen peaks obtained using the 254-nm detector.Calculate the quantity,in mg,of propoxyphene hydrochloride (C22H29NO2·HCl)in the portion of Tablets taken by the formula:
200C(rU/rS),
in which Cis the concentration,in µg per mL,of USP Propoxyphene Hydrochloride RSin Standard preparation 1,and rUand rSare the propoxyphene hydrochloride peak responses obtained from Assay preparation 1and Standard preparation 1,respectively.Calculate the quantity,in mg,of acetaminophen (C8H9NO2)in the portion of Tablets taken by the formula:
4000C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Acetaminophen RSin Standard preparation 2,and rUand rSare the acetaminophen peak responses obtained from Assay preparation 2and Standard preparation 2,respectively.
Auxiliary Information— Staff Liaison:Daniel K.Bempong,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28–NF23Page 1652
Pharmacopeial Forum:Volume No.30(1)Page 170
Phone Number:1-301-816-8143