Paroxetine Tablets
(Title for this new monograph—to become official February 1,2006)USP28
»Paroxetine Tablets contain an amount of Paroxetine Hydrochloride equivalent to not less than 90.0percent and not more than 110.0percent of the labeled amount of paroxetine (C19H20FNO3).
Packaging and storage— Preserve in tight containers,and store at controlled room temperature.
Identification—
A:Infrared Absorption á197Kñ—
Test specimen— Transfer an amount of finely powdered Tablets,equivalent to about 90mg of paroxetine,to a suitable flask,add 100mLof 0.1Nhydrochloric acid,and stir for 1hour.Transfer the mixture to a separatory funnel,and add ammonium hydroxide until the solution is alkaline to litmus paper.Add 100mLof ethyl ether to the funnel,and shake for 2minutes.Transfer the organic layer into the necessary number of centrifuge tubes,and centrifuge for 10minutes.Recombine the clarified extracts,add 1drop of water and 0.5mLof 0.1Nhydrochloric acid,stir,and evaporate to dryness under a stream of nitrogen.Dry the residue in an oven at 90for 1hour.
B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
C: Place a quantity of finely powdered Tablets,equivalent to about 450mg of paroxetine,in a stoppered flask.Add 100mLof alcohol,and shake for 1hour.Centrifuge about 20mLof the mixture,and measure the angular rotation of the supernatant at 20(see Optical Rotation á781ñ):the angular rotation is between –75and –115.
Dissolution á711ñ—
Medium: simulated gastric fluid without enzyme;900mL.
Apparatus 2: 60rpm.
Time: 60minutes.
Determine the amount of C19H20FNO3dissolved by employing the following method.
Buffer solution andMobile phase— Prepare as directed in the Assay.
Standard stock solution— Dissolve an accurately weighed quantity of USP Paroxetine Hydrochloride RSin an amount of methanol not exceeding 5%of the volume of the final solution,and dilute with Mediumto obtain a solution having a known concentration of about 0.63mg per mL.
Standard solution— Quantitatively dilute the Standard stock solutionwith Mediumto obtain a solution having a concentration estimated to correspond to that of the filtered solution under test.
Chromatographic system— Proceed as directed in the Assay,except to chromatograph the Standard solution.
Procedure— Separately inject equal volumes (about 20µL)of a portion of the solution under test,previously passed through a suitable 0.45-µm membrane filter,and the Standard solutioninto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity of C19H20FNO3dissolved based on the peak responses obtained from the solution under test and the Standard solution.
Tolerances— Not less than 80%(Q)of the labeled amount of C19H20FNO3is dissolved in 60minutes.
Uniformity of dosage units á905ñ: meet the requirements.
PROCEDURE FOR CONTENT UNIFORMITY—
Buffer solution,Mobile phase,and Chromatographic system— Proceed as directed in the Assay.
Standard solution— Use the Standard preparation,prepared as directed in the Assay.
Test solution— Place 1Tablet in a suitable volumetric flask,and add a volume of a hydrochloric acid solution (7in 1000),equivalent to about 25%of the flask volume.Allow the Tablet to disintegrate,dilute with methanol to volume,and mix to obtain a solution containing about 0.1mg of paroxetine per mL.Centrifuge a portion of the solution.
Procedure— Proceed as directed in the Assay.Calculate the quantity,in mg,of C19H20FNO3in the Tablet taken by the formula:
VC(329.37/365.83)(rU/rS),
in which Vis the volume of the flask used;rUand rSare the peak responses obtained from the Test solutionand the Standard solution,respectively;and the other terms are as defined therein.
Assay—
Buffer solution— Prepare a mixture of water,phosphoric acid,and triethylamine (100:0.6:0.3).
Mobile phase— Prepare a filtered and degassed mixture of Buffer solutionand acetonitrile (7:3).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Paroxetine Hydrochloride RSin methanol,and dilute quantitatively,and stepwise if necessary,with methanol to obtain a solution having a known concentration of about 0.1mg per mL.
Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 100mg of paroxetine,to a 200-mLvolumetric flask,dissolve in and dilute with methanol to volume,and mix.Centrifuge a portion of this solution for 6minutes.Transfer 20mLof the supernatant to a 100-mLvolumetric flask,dilute with methanol to volume,and mix.
Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 295-nm detector and a 4.6-mm ×3.3-cm column that contains 3-µm packing L7.The flow rate is about 2.0mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency is not less than 750theoretical plates;the tailing factor is not more than 4;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 5µL)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 paroxetine (C19H20FNO3)in the portion of Tablets taken by the formula:
1000C(329.37/365.83)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Paroxetine Hydrochloride RSin the Standard preparation;329.37and 365.83are the molecular weights for paroxetine and paroxetine hydrochloride,respectively;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 1476
Pharmacopeial Forum:Volume No.30(3)Page 919
Phone Number:1-301-816-8165