»Letrozole Tablets contain not less than 95.0percent and not more than 105.0percent of the labeled amount of letrozole (C17H11N5).
Packaging and storage Preserve in tight containers at controlled room temperature.
A: Thin-Layer Chromatographic Identification Test á201ñ
Test solution Transfer a quantity of finely powdered Tablets,equivalent to about 5mg of letrozole,to a centrifuge tube,add 2.5mLof methanol,shake thoroughly,sonicate for 10minutes,and centrifuge.
Application volume: 5µL.
Developing solvent system: a mixture of ethyl acetate and methanol (9:1).
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.
Medium: 0.1Nhydrochloric acid;500mL.
Apparatus 2: 75rpm.
Determine the amount of C17H11N5dissolved by employing the following method.
Mobile phase and Chromatographic systemPrepare as directed in the Assay.
Procedure Inject a volume (about 200µL)of a filtered portion of the solution under test into the chromatograph,record the chromatogram,and measure the responses for the major peaks.Calculate the quantity,in mg,of C17H11N5dissolved in comparison with a Standard solution having a known concentration of USP Letrozole RSin the same Mediumand similarly chromatographed.
Tolerances Not less than 80%(Q)of the labeled amount of C17H11N5is dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements.
PROCEDURE FOR CONTENT UNIFORMITY
Diluent,Mobile phase,System suitability solution,andChromatographic system Proceed as directed in the Assay.
Standard solution Prepare as directed for the Standard preparationin the Assay.
Test solution Place 1Tablet in a 250-mLvolumetric flask,add about 15mLof Mobile phase,and shake to dissolve.Dilute with Mobile phaseto volume,mix,and centrifuge a portion of the solution.
Procedure Proceed as directed in the Assay.Calculate the quantity,in mg,of letrozole (C17H11N5)in the Tablet taken by the formula:
250C(rU/rS),in which Cis the concentration,in mg per mL,of USP Letrozole RSin the Standard solution;and rUand rSare the letrozole peak responses obtained from the Test solutionand the Standard solution,respectively.
Solution A,Solution B,Mobile phase,andDiluent Prepare as directed in the Assayunder Letrozole.
System suitability solution,Reference solution,andChromatographic system Proceed as directed in the test for Related compoundsunder Letrozole,except to use an injection volume of 50µL.
Test solution Place a number of Tablets,equivalent to about 25mg of letrozole,in a 250-mLvolumetric flask.Add 150mLof Diluent,shake for 15minutes,dilute with Diluentto volume,and mix.Centrifuge a portion of this solution,and dilute an accurately measured volume of it with Diluentto obtain a solution containing about 10µg of letrozole per mL.
Procedure Proceed as directed in the test for Related compoundsunder Letrozole,except to use an injection volume of 50µL.Calculate the percentage of each letrozole related compound in the Tablets,disregarding any values obtained that are less than 0.05%:not more than 0.3%of letrozole related compound Ais found;not more than 0.2%of 4,4¢,4¢¢-methylidenetrisbenzonitrile is found;not more than 0.1%of any other impurity is found;and not more than 0.3%of all other impurities is found.
Diluent Prepare a filtered and degassed mixture of water and acetonitrile (7:3).
Mobile phase Prepare a filtered and degassed mixture of water and acetonitrile (13:12).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
System suitability solution Prepare as directed in the Related compoundstest under Letrozole.
Standard preparation Prepare as directed in the Assayunder Letrozole.
Assay preparation Place a number of Tablets,equivalent to about 50mg of letrozole,in a 250-mLvolumetric flask.Add about 20mLof water,and shake for 5minutes to dissolve the Tablets.Add 75mLof acetonitrile,shake for 30minutes,and dilute with water to volume.Centrifuge a portion of the solution.Dilute an accurately measured volume of this solution with Diluent,to obtain a solution containing about 10µg of letrozole per mL.
Chromatographic system(see Chromatography á621ñ) The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm ×12.5-cm column that contains 5-µm packing L1.The flow rate is about 1.0mLper minute.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.68for letrozole related compound Aand 1.0for letrozole;and the resolution,R,between letrozole related compound Aand letrozole is not less than 1.5.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor is between 0.8and 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 areas for the major peaks.Calculate the quantity,in mg,of letrozole (C17H11N5)in the portion of Tablets taken by the formula:
5000C(rU/rS),in which Cis the concentration,in mg per mL,of USP Letrozole RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28NF23Page 1113Pharmacopeial Forum:Volume No.28(1)Page 71