Acebutolol Hydrochloride Capsules
»Acebutolol Hydrochloride Capsules contain the equivalent of not less than 90.0percent and not more than 110.0percent of the labeled amount of acebutolol (C18H28N2O4).
Packaging and storage— Preserve in tight containers,and store at controlled room temperature.
Identification— The retention time of the major peak in the chromatogram of theAssay preparationcorresponds to that in the chromatogram of theStandard preparation,as obtained in theAssay.
Dissolution á711ñ—
Medium: water;900mL.
Apparatus 2: 50rpm.
Time: 30minutes.
Procedure— Determine the amount of C18H28N2O4dissolved by employing UVabsorption at the wavelength of maximum absorbance at about 232nm on filtered portions of the solution under test in comparison with a Standard solution having a known concentration of USP Acebutolol Hydrochloride RSin the sameMedium.
Tolerances— Not less than 80%(Q)of the labeled amount of acebutolol (C18H28N2O4)is dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Chromatographic purity—
TEST1—
Buffer solution— Prepare as directed in theAssay.
Mobile phase— Prepare a filtered and degassed mixture ofBuffer solutionand methanol (56:44).Make adjustments if necessary (seeSystem SuitabilityunderChromatography á621ñ).
Diluent— Prepare a mixture of Buffer solutionand methanol (50:50).
Standard solution— Transfer about 30mg of USP Acebutolol Hydrochloride RS,accurately weighed,to a 50-mLvolumetric flask.Add about 12mLof methanol,swirl to dissolve,dilute withDiluentto volume,and mix.Dilute an accurately measured volume of this solution quantitatively,and stepwise if necessary,withDiluentto obtain a solution having a known concentration of about 1.4µg of USP Acebutolol Hydrochloride RSper mL.
Test solution— Transfer an accurately weighed portion of the contents of 20opened Capsules,equivalent to about 250mg of acebutolol,to a 100-mLvolumetric flask,add about 25mLof methanol,and shake by mechanical means for about 15minutes.Dilute withDiluentto volume,and mix.Centrifuge a portion of this solution,and transfer 10.0mLof the clear supernatant to a 100-mLvolumetric flask.Dilute withDiluentto volume,and mix.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 240-nm detector and a 3.9-mm ×15-cm column that contains 4-µm packing L1.The flow rate is about 1mLper minute.Chromatograph theStandard solution,and record the peak responses as directed forProcedure:the relative standard deviation for replicate injections is not more than 6.0%.
Procedure— Separately inject equal volumes (about 35µL)of theStandard solution,Test solution,andDiluentinto the chromatograph,record the chromatograms for about two times the retention time of acebutolol,and measure the responses for all the peaks,disregarding any peaks corresponding to those obtained from theDiluent.Calculate the percentage of each impurity eluting prior to the acebutolol peak in the portion of Capsules taken by the formula:
(336.44/372.89)(0.4C)(ri/rS),
in which 336.44and 372.89are the molecular weights of acebutolol and acebutolol hydrochloride,respectively;Cis the concentration,in µg per mL,of USP Acebutolol Hydrochloride RSin theStandard solution;riis the peak response of any individual impurity obtained from theTest solution;and rSis the peak response of acebutolol obtained from theStandard solution:not more than 0.5%of any individual impurity is found.
TEST2—
Buffer solution— Prepare as directed in theAssay.
Mobile phase— Prepare a filtered and degassed mixture ofBuffer solutionand methanol (50:50).Make adjustments if necessary (seeSystem Suitability underChromatography á621ñ).
Standard solution— Transfer about 30mg of USP Acebutolol Hydrochloride RS,accurately weighed,to a 50-mLvolumetric flask.Add about 12mLof methanol,swirl to dissolve,dilute withMobile phaseto volume,and mix.Dilute an accurately measured volume of this stock solution quantitatively,and stepwise if necessary,withMobile phaseto obtain a solution having a known concentration of about 1.4µg of USP Acebutolol Hydrochloride RSper mL.
Test solution— Transfer an accurately weighed portion of the contents of 20opened Capsules,equivalent to about 250mg of acebutolol,to a 100-mLvolumetric flask,add about 25mLof methanol,and shake by mechanical means for about 15minutes.Dilute withMobile phaseto volume,and mix.Centrifuge a portion of this solution,and transfer 10.0mLof the clear supernatant to a 100-mLvolumetric flask.Dilute withMobile phaseto volume,and mix.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 240-nm detector and a 3.9-mm ×15-cm column that contains 4-µm packing L1.The flow rate is about 1mLper minute.Chromatograph theStandard solution,and record the peak responses as directed forProcedure:the relative standard deviation for replicate injections is not more than 6.0%.
Procedure— Separately inject equal volumes (about 70µL)of theStandard solution,Test solution,andMobile phaseinto the chromatograph,record the chromatograms for about three times the retention time of acebutolol,and measure the responses for all the peaks,disregarding any peaks corresponding to those obtained from theMobile phase.Calculate the percentage of each impurity eluting after the acebutolol peak in the portion of Capsules taken by the formula:
(336.44/372.89)(0.4C)(ri/rS),
in which 336.44and 372.89are the molecular weights of acebutolol and acebutolol hydrochloride,respectively;Cis the concentration,in µg per mL,of USP Acebutolol Hydrochloride RSin theStandard solution;riis the peak response of any individual impurity obtained from theTest solution;and rSis the peak response of acebutolol obtained from theStandard solution:not more than 0.5%of any individual impurity is found.The sum of all individual impurities found inTest 1andTest 2is not more than 1.0%.
Assay—
Buffer solution— Dissolve about 2.4g of sodium 1-decanesulfonate in 1000mLof water.Adjust with glacial acetic acid to a pHof 3.5.
Mobile phase— Prepare a filtered and degassed mixture of methanol andBuffer solution(60:40).Make adjustments if necessary (seeSystem SuitabilityunderChromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Acebutolol Hydrochloride RSquantitatively in methanol to obtain a solution having a known concentration of about 0.22mg per mL.This is equivalent to about 0.2mg of acebutolol per mL.
Assay preparation— Weigh and mix,as completely as possible,the contents of not fewer than 20Capsules.Transfer an accurately weighed portion of the powder,equivalent to about 200mg of acebutolol,to a 200-mLvolumetric flask.Add about 180mLof methanol,and stir by mechanical means for about 30minutes.Dilute with methanol to volume,and mix.Transfer 5.0mLof this solution to a 25-mLvolumetric flask,dilute with methanol to volume,and mix.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×15-cm column that contains 5-µm packing L1.The flow rate is about 1mLper minute.Chromatograph theStandard preparation,and record the peak responses as directed forProcedure:the tailing factor is not more than 1.5;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20µL)of theStandard preparationand theAssay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of acebutolol (C18H28N2O4)in the portion of Capsules taken by the formula:
(336.44/372.89)(1000C)(rU/rS),
in which 336.44and 372.89are the molecular weights of acebutolol and acebutolol hydrochloride,respectively;Cis the concentration,in mg per mL,of USP Acebutolol Hydrochloride RSin theStandard preparation;and rUand rSare the acebutolol peak responses obtained from theAssay preparationand theStandard preparation,respectively.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 13
Pharmacopeial Forum:Volume No.28(1)Page 33
Phone Number:1-301-816-8305