» Letrozole Tablets contain not less than 95.0 percent and not more than 105.0 percent of the labeled amount of letrozole (C17H11N5).
Packaging and storage Preserve in tight containers at controlled room temperature.
A: Thin-Layer Chromatographic Identification Test 201
Test solution Transfer a quantity of finely powdered Tablets, equivalent to about 5 mg of letrozole, to a centrifuge tube, add 2.5 mL of methanol, shake thoroughly, sonicate for 10 minutes, and centrifuge.
Application volume: 5 µL.
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 preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Medium: 0.1 N hydrochloric acid; 500 mL.
Apparatus 2: 75 rpm.
Time: 30 minutes.
Determine the amount of C17H11N5 dissolved by employing the following method.
Mobile phase and Chromatographic systemPrepare as directed in the Assay.
Procedure Inject a volume (about 200 µL) 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 C17H11N5 dissolved in comparison with a Standard solution having a known concentration of USP Letrozole RS in the same Medium and similarly chromatographed.
Tolerances Not less than 80% (Q) of the labeled amount of C17H11N5 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
procedure for content uniformity
Diluent, Mobile phase, System suitability solution, and Chromatographic system Proceed as directed in the Assay.
Standard solution Prepare as directed for the Standard preparation in the Assay.
Test solution Place 1 Tablet in a 250-mL volumetric flask, add about 15 mL of Mobile phase, and shake to dissolve. Dilute with Mobile phase to 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 C is the concentration, in mg per mL, of USP Letrozole RS in the Standard solution; and rU and rS are the letrozole peak responses obtained from the Test solution and the Standard solution, respectively.
Solution A, Solution B, Mobile phase, and Diluent Prepare as directed in the Assay under Letrozole.
System suitability solution, Reference solution, and Chromatographic system Proceed as directed in the test for Related compounds under Letrozole, except to use an injection volume of 50 µL.
Test solution Place a number of Tablets, equivalent to about 25 mg of letrozole, in a 250-mL volumetric flask. Add 150 mL of Diluent, shake for 15 minutes, dilute with Diluent to volume, and mix. Centrifuge a portion of this suspension, and use a portion of the clear supernatant for injection.
Procedure Proceed as directed in the test for Related compounds under Letrozole, except to use an injection volume of 50 µL. 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 A is 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 Suitability under Chromatography 621).
System suitability solution Prepare as directed in the Related compounds test under Letrozole.
Standard preparation Prepare as directed in the Assay under Letrozole.
Assay preparation Place a number of Tablets, equivalent to about 50 mg of letrozole, in a 250-mL volumetric flask. Add about 20 mL of water, and shake for 5 minutes to dissolve the Tablets. Add 75 mL of acetonitrile, shake for 30 minutes, 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 10 µg of letrozole per mL.
Chromatographic system (see Chromatography 621) 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 1.0 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.68 for letrozole related compound A and 1.0 for letrozole; and the resolution, R, between letrozole related compound A and 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 0.8 and 1.5; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into 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 C is the concentration, in mg per mL, of USP Letrozole RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP32NF27 Page 2757Pharmacopeial Forum: Volume No. 33(2) Page 244