A: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that of the Standard preparationas obtained in the Assay.

B: It responds to the Thin-Layer Chromatographic Identification Test á201ñ,the test solution and the Standard solution being prepared at a concentration of 2mg per mLin methanol,and a solvent system consisting of a mixture of ethyl acetate,glacial acetic acid,and water (5:2:2)being used.

Medium: water;500mL.

Apparatus 2: 50rpm.

Time: 45minutes.

Procedure— Determine the amount of C9H9Cl2N3Odissolved,employing the procedure set forth in the Assayand making any necessary modifications.

Tolerances— Not less than 75%(Q)of the labeled amount of C9H9Cl2N3Ois dissolved in 45minutes.

pH2.5Diethylamine phosphate solution— Add 10.3mLof diethylamine to about 70mLof water.Adjust with phosphoric acid to a pHof 2.5,dilute with water to 100mL,and mix.

Reagent solution— Dissolve an accurately weighed quantity of 2,6-dichlorophenylacetic acid in Mobile phase,and dilute quantitatively,and stepwise if necessary,to obtain a solution having a known concentration of about 18µg per mL.

Mobile phase— Dissolve 600mg of monobasic potassium phosphate and 3mLof pH2.5Diethylamine phosphate solutionin 480mLof water,and mix.Adjust with 0.2Nsodium hydroxide to a pHof 4.0.While swirling,add 520mLof acetonitrile.Filter and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Internal standard solution— Prepare a solution of butylparaben in Mobile phasecontaining 0.5mg per mL.

Standard preparation— Dissolve an accurately weighed quantity of USP Guanfacine Hydrochloride RSin Mobile phaseto obtain a solution having a known concentration of about 0.23mg per mL.Transfer 5.0mLof this solution to a 25-mLvolumetric flask,and add 5.0mLeach of the Reagent solutionand the Internal standard solution.Dilute with Mobile phaseto volume,and mix.

Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 10mg of guanfacine,to a 100-mLvolumetric flask.Add 50mLof Mobile phase,and heat on a steam bath for 5minutes.Cool to room temperature,dilute with Mobile phaseto volume,and mix.Transfer 10.0mLof this solution to a 25-mLvolumetric flask,add 5.0mLof Internal standard solution,dilute with Mobile phaseto volume,and mix.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 220-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.4for guanfacine,0.6for 2,6-dichlorophenylacetic acid,and 1.0for butylparaben;the resolution,R,between guanfacine and 2,6-dichlorophenylacetic acid is not less than 1.5,and the resolution,R,between 2,6-dichlorophenylacetic acid and butylparaben is not less 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 the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of guanfacine (C9H9Cl2N3O)in the portion of Tablets taken by the formula: in which 246.09and 282.55are the molecular weights of guanfacine and guanfacine hydrochloride,respectively;Cis the concentration,in µg per mL,of USP Guanfacine Hydrochloride RSin the Standard preparation;and RUand RSare the peak response ratios of guanfacine to butylparaben obtained from the Assay preparationand the Standard preparation,respectively.