Guanabenz Acetate Tablets
»Guanabenz Acetate Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amount of guanabenz (C8H8N4Cl2).
Packaging and storage— Preserve in tight,light-resistant containers.
Identification— Transfer an amount of powdered Tablets,equivalent to about 8mg of guanabenz,to a 60-mLseparator.Add 10mLof 0.1Nhydrochloric acid,and shake to disperse the powder.Shake the mixture with three 10-mLportions of chloroform,discarding the chloroform phase each time.Add 5mLof 1Nsodium hydroxide,and extract with two 25-mLportions of ether,filtering the ether extracts.Evaporate the combined extracts with the aid of a current of air to dryness:the IRabsorption spectrum of a potassium bromide dispersion of the residue so obtained exhibits maxima at the same wavelengths as that of a similar preparation of USP Guanabenz Acetate RS.
Dissolution á711ñ—
Medium: water;1000mL.
Apparatus 2: 50rpm.
Time: 60minutes.
Procedure— Determine the amount of C8H8N4Cl2dissolved from UVabsorbances at the wavelength of maximum absorbance at about 272nm of filtered portions of the solution under test,suitably diluted with Medium,in comparison with a Standard solution having a known concentration of USP Guanabenz Acetate RSin the same medium.
Tolerances— Not less than 75%(Q)of the labeled amount of C8H8N4Cl2is dissolved in 60minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Chromatographic purity—
Extracting solvent,Mobile phase,Standard preparation I,System suitability solution,Chromatographic system,and Assay preparation— Proceed as directed in the Assay.
Standard preparation II— Pipet 2mLof Standard preparation Iinto a 100-mLvolumetric flask,dilute with Extracting solventto volume,and mix.
Procedure— Proceed as directed for Procedurein the Assay,except to substitute Standard preparation IIfor Standard preparation I.Calculate the quantity of any impurity observed having a relative retention time corresponding to the component eluting before guanabenz obtained from the System suitability solution.The amount of any such impurity observed is not more than 2%.
Assay—
Extracting solvent— Dissolve 8.2g of sodium acetate in 20mLof water,add 5.7mLof glacial acetic acid,dilute to 1Lwith methanol,and mix.
Mobile phase— Prepare a filtered and degassed mixture of water,methanol,and phosphoric acid (57:43:0.3),making adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation I— Transfer about 25mg of USP Guanabenz Acetate RS,accurately weighed,to a 250-mLvolumetric flask.Add 25mLof water,shake to dissolve the solids,dilute with Extracting solventto volume,and mix.
Assay preparation— Transfer 10Tablets to a 500-mLvolumetric flask.Add 50mLof water,stir by mechanical means until the solids are well dispersed,add 400mLof Extracting solvent,and stir for 45minutes.Dilute with Extracting solventto volume,mix,and centrifuge a portion of the mixture until a clear supernatant is obtained.If necessary,dilute a portion of the supernatant quantitatively with a mixture of Extracting solventand water (9:1)to obtain a solution containing about 0.08mg of guanabenz per mL.
System suitability solution— Transfer about 30mg of guanabenz acetate to a 100-mLstoppered flask.Add about 50mLof 0.1Nhydrochloric acid,heat on a steam bath for 60minutes,and allow the solution to cool.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 245-nm detector and a 4-mm ×30-cm column that contains packing L1.The flow rate is about 2mLper minute.Chromatograph replicate injections of Standard preparation Iand record the peak responses as directed for Procedure:the relative standard deviation is not more than 2.0%.Inject a volume (about 20µL)of the System suitability solutioninto the chromatograph and record the chromatogram:the resolution between guanabenz and the peak eluting before it is not less than 1.6.
Procedure— Separately inject equal volumes (about 20µL)of Standard preparation Iand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C8H8N4Cl2in the portion of Tablets taken by the formula:
(231.08/291.13)(CD)(rU/rS),
in which 231.08and 291.13are the molecular weights of guanabenz and guanabenz acetate,respectively;Cis the concentration,in mg per mL,of USP Guanabenz Acetate RSin Standard preparation I;Dis the Assay preparationdilution factor,in mLper Tablet;and rUand rSare the peak responses of the Assay preparationand Standard preparation I,respectively.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 930
Phone Number:1-301-816-8305