»Letrozole contains not less than 98.0percent and not more than 102.0percent of C17H11N5,calculated on the anhydrous basis.
Packaging and storage Preserve in tight containers at controlled room temperature.
A: Infrared Absorption á197Mñ.
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.
Water,Method Iá921ñ: not more than 0.3%.
Residue on ignition á281ñ: not more than 0.1%.
Heavy metals,Method IIá231ñ: 0.001%.
Solution A,Solution B,Mobile phase,andDiluent Prepare as directed in the Assay.
System suitability solution Dissolve accurately weighed quantities of USP Letrozole Related Compound A RSand USP Letrozole RSin Diluentto obtain a solution having known concentrations of about 2µg per mLand 10µg per mL,respectively.
Test solution Transfer about 25mg of Letrozole,accurately weighed,to a 250-mLvolumetric flask,dissolve in 75mLof acetonitrile,dilute with water to volume,and mix.
Reference solution Transfer 5.0mLof the Test solutionto a 50-mLvolumetric flask,and dilute with Diluentto volume.Transfer 5.0mLof the solution so obtained to a 50-mLvolumetric flask,dilute with Diluentto volume,and mix.
Chromatographic system Prepare as directed in the Assay.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 Reference solution,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 10.0%.
Procedure [NOTE4,4¢,4¢¢-Methylidenetrisbenzonitrile may be present;its relative retention time is about 1.9.]Separately inject equal volumes (about 15µL)of the Test solutionand the Reference solutioninto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the percentage of each impurity in the portion of Letrozole taken by the formula:
ri/rR,in which riis the peak response of letrozole related compound A,4,4¢,4¢¢-methylidenetrisbenzonitrile,or any other impurity obtained from the Test solution;and rRis the peak response of letrozole obtained from the Reference solution: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.
Organic volatile impurities,Method Vá467ñ: meets the requirements.
Solvent: dimethyl sulfoxide.
Solution A Use filtered and degassed water.
Solution B Use filtered and degassed acetonitrile.
Mobile phase Use variable mixtures of Solution Aand Solution Bas directed for Chromatographic system.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Diluent Prepare a filtered and degassed mixture of Solution Aand Solution B(7:3).
Standard preparation Dissolve an accurately weighed quantity of USP Letrozole RSin Diluent,and dilute quantitatively,and stepwise if necessary,with Diluentto obtain a solution having a known concentration of about 10µg per mL.
Assay preparation Transfer about 20mg of Letrozole,accurately weighed,to a 100-mLvolumetric flask.Dissolve in and dilute with Diluentto volume,and mix.Pipet 5.0mLof this solution into a 100-mLvolumetric flask,dilute with Diluentto volume,and mix.
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.The chromatograph is programmed as follows.
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 C17H11N5in the portion of Letrozole taken by the formula:
2000C(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 1112Pharmacopeial Forum:Volume No.27(6)Page 3313