Protriptyline Hydrochloride Tablets
»Protriptyline Hydrochloride Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amount of C19H21N·HCl.
Packaging and storage— Preserve in tight containers.
Identification—
A: 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.
B: Afiltered solution of finely powdered Tablets,equivalent to protriptyline hydrochloride solution (1in 20),meets the requirements of the tests for Chloride á191ñ,when tested as specified for alkaloidal hydrochlorides.
Dissolution á711ñ—
Medium: water;900mL.
Apparatus 1: 100rpm.
Time: 45minutes.
Procedure— Determine the amount of C19H21N·HCl dissolved from UVabsorbances at the wavelength of maximum absorbance at about 290nm of filtered portions of the solution under test,suitably diluted with Dissolution Medium,if necessary,in comparison with a Standard solution having a known concentration of USP Protriptyline Hydrochloride RSin the same medium.
Tolerances— Not less than 75%(Q)of the labeled amount of C19H21N·HCl is dissolved in 45minutes.
Uniformity of dosage units á905ñ: meet the requirements.
PROCEDURE FOR CONTENT UNIFORMITY—
Solution A ,Solution B,Mobile phase,Diluent,Standard preparation,and Chromatographic system—Proceed as directed in the Assay.
Test preparation— Transfer 1finely powdered Tablet to a 50-mLvolumetric flask,add about 1mLof 2.5Nhydrochloric acid and 5mLof water for each 5mg of protriptyline hydrochloride,and shake by mechanical means for 20minutes or until the Tablet is fully disintegrated.Add 5mLof alcohol for each 5mg of protriptyline hydrochloride,and shake for an additional 10minutes.Dilute with water to volume,mix,and pass through a 0.45-µm membrane filter,discarding the first 1.5mLof the filtrate.Use the subsequent filtrate as the Test preparation.
Procedure— Proceed as directed in the Assay.Calculate the quantity,in mg,of protriptyline hydrochloride (C19H21N·HCl)in the Tablet taken by the formula:
(TC/D)(rU/rS),
in which Tis the labeled quantity,in mg,of protriptyline hydrochloride in the Tablet;Cis the concentration,in µg per mL,of USP Protriptyline Hydrochloride RSin the Standard preparation;Dis the concentration,in µg per mL,of protriptyline hydrochloride in the Test preparation,based on the labeled quantity per Tablet and the extent of dilution;and rUand rSare the peak responses obtained from the Test preparationand the Standard preparation,respectively.
Assay—
Solution A— Prepare a filtered and degassed solution of 22.0g of monobasic sodium phosphate and 3.78g of sodium 1-hexanesulfonate in 1900mLof water.Adjust with phosphoric acid to a pHof 2.90,and dilute with water to volume in a 2000-mLvolumetric flask.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Solution B— Use filtered and degassed acetonitrile.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Mobile phase— Use variable mixtures of Solution Aand Solution Bas directed for Chromatographic system.
Diluent— Add 200mLof alcohol to a 1000-mLvolumetric flask.Add 40mLof 2.5Nhydrochloric acid,dilute with water to volume,and mix.
Standard preparation— Dissolve an accurately weighed quantity of USP Protriptyline Hydrochloride RSin Diluent,and dilute quantitatively,and stepwise if necessary,with Diluentto obtain a solution having a known concentration of about 0.20mg per mL.
Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 40mg of protriptyline hydrochloride,to a 200-mLvolumetric flask,add 40mLof alcohol,and shake by mechanical means for 5minutes.Add 40mLof water and 8mLof 2.5Nhydrochloric acid,and shake for an additional 10minutes.Dilute with water to volume,and mix.Pass through a 0.45-µm membrane filter,discarding the first 5mLof the filtrate.Use the subsequent filtrate as the Assay preparation.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 280-nm detector and a 4.6-mm ×15-cm column containing 5-µm base-deactivated packing L7.The flow rate is about 1.5mLper minute.The chromatograph is programmed as follows.
Time
(minutes)		 Solution A
(%)		 Solution B
(%)		 Elution
0 83 17 equilibration
0-15 83®50 17®50 linear gradient
15-20 50 50 isocratic
20-25 50®83 50®17 linear gradient
25-30 83 17 re-equilibration
Chromatograph the Standard preparationand record the peak responses as directed for Procedure:the column efficiency is not less than 25,000theoretical plates;the tailing factor is not more than 2.5;and the relative standard deviation is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20µL)of the Assay preparationand the Standard preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of protriptyline hydrochloride (C19H21N·HCl)in the portion of Tablets taken by the formula:
200C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Protriptyline Hydrochloride RSin the Standard preparation;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 1670
Phone Number:1-301-816-8165