Levothyroxine Sodium Tablets
»Levothyroxine Sodium Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amount of levothyroxine sodium (C15H10I4NNaO4).
Packaging and storage— Preserve in tight,light-resistant containers.
Labeling— When more than oneDissolution test is given,the labeling states theDissolution test used only ifTest 1is not used.
Identification—
Solvent system— Mix 5volumes of tert-amyl alcohol,4volumes of water,and 1volume of ammonium hydroxide,shake,and allow to stand.Transfer the upper phase to a suitable chromatographic chamber arranged for thin-layer chromatography,pouring it over the paper lining,cover the chamber,and allow to stand for 1hour.
Detection reagent— Add 65mLof 2Nhydrochloric acid to 50mLof a 1in 10solution of sodium arsenite in 1Nsodium hydroxide,with vigorous stirring.Mix 1volume of this solution with 5volumes of a 27in 1000solution of ferric chloride in 2Nhydrochloric acid and 5volumes of freshly prepared potassium ferricyanide solution (35in 1000).
Standard solution— Prepare a solution of about 15mg of USP Levothyroxine RS,accurately weighed,in 100mLof a mixture of 19volumes of methanol and 1volume of ammonium hydroxide.Dilute 10.0mLof this solution with the same solvent to 50.0mL,and mix.
Test solution— Shake an amount of powdered Tablets,equivalent to about 60µg of levothyroxine sodium,with 2mLof a mixture of 19volumes of methanol and 1volume of ammonium hydroxide in a centrifuge tube for 10minutes,and centrifuge.
Procedure— Apply 10-µLvolumes of theTest solution and of theStandard solution,respectively,to a thin-layer chromatographic plate coated with a 0.1-mm layer of cellulose.Develop the plate in theSolvent system until the solvent front has moved not less than 10cm beyond the point of application of theTest solution,air-dry,and spray the plate withDetection reagent:the chromatogram of theTest solution shows a blue spot corresponding inRFvalue to the chromatogram from the levothyroxineStandard solution.
Change to read:
Dissolution á711ñ— [NOTE—All containers that are in contact with solutions containing levothyroxine sodium are to be made of glass.USP28]
TEST1—
Medium: 0.01Nhydrochloric acid containing 0.2%sodium lauryl sulfate;500mL.
Apparatus 2: 50rpm.
Time: 45minutes.
Determine the amount of C15H10I4NNaO4dissolved by employing the following method.
Mobile phase— Prepare a filtered and degassed mixture of methanol and 0.1%phosphoric acid (60:40).Make adjustments if necessary (see System Suitability under Chromatography á621ñ).
Standard solution— Prepare a stock solution of USP Levothyroxine RSin methanol having a known concentration of about 0.1mg per mL.Dilute this stock solution with Medium to obtain a solution having a concentration similar to that expected in theTest solution.
Test solution— [NOTE—Prior to use,check the filters for absorptive loss of drug.]Use a filtered portion of the solution under test.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 225-nm detector and a 4.6-mm ×25-cm column that contains packing L1.The flow rate is about 2mLper minute.Chromatograph theStandard solution,and record the peak responses as directed forProcedure:the tailing factor is not more than 1.5;and the relative standard deviation is not more than 4.0%.
Procedure— Separately inject equal volumes (about 800µL)of theStandard solution and theTest solution into the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the amount of C15H10I4NNaO4dissolved.
Tolerances— Not less than 70%(Q)of the labeled amount of C15H10I4NNaO4is dissolved in 45minutes.
TEST2— If the product complies with this test,the labeling indicates that it meets USPDissolution Test 2.
Medium,Apparatus,Mobile phase,Standard solution,Test solution,Chromatographic system,and Procedure— Proceed as directed forTest 1.
Time: 15minutes.
Tolerances— Not less than 80%(Q)of the labeled amount of C15H10I4NNaO4is dissolved in 15minutes.
TEST4— If the product complies with this test,the labeling indicates that it meets USPDissolution Test 4.
NOTE—Do not use paddle stirrers with synthetic coating.
USP28
Medium: 0.01Nhydrochloric acid;500mLfor tablets labeled to contain between 25µg and 175µg of levothyroxine sodium;900mLfor tablets labeled to contain 200µg or 300µg of levothyroxine sodium.
Apparatus 2: 75rpm.
Time: 45minutes.
Determine the amount of C15H10I4NNaO4dissolved by employing the following method.
Mobile phase— Prepare a filtered and degassed mixture of water,acetonitrile,and 85%orthophosphoric acid (700:500:2).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard solution— Prepare a stock solution by transferring about 100mg of USP Levothyroxine RS,accurately weighed,to a 100-mLvolumetric flask.Add 80mLof alcohol and 1mLof 1Nhydrochloric acid,sonicate for about 2minutes,dilute with alcohol to volume,and mix.Dilute this stock solution with a mixture of alcohol and water (1:1)to obtain a solution having a concentration of 0.01mg of levothyroxine per mL.Dilute this intermediate solution with Mediumto obtain a solution having a concentration similar to that expected in the Test solution.
Test solution— Use a centrifuged portion of the solution under test.
Chromatographic system (seeChromatography á621ñ)— The liquid chromatograph is equipped with a 225-nm detector and a 4.0-mm ×12.5-cm column that contains packing L7.The flow rate is about 1.5mLper minute.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the tailing factor is not more than 1.5;and the relative standard deviation is not more than 4.0%.
Procedure— Separately inject equal volumes (about 500µL)of the Standard solutionand the Test solution into the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the amount of C15H10I4NNaO4.
Tolerances— Not less than 80%(Q)of the labeled amount of C15H10I4NNaO4is dissolved in 45minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Limit of liothyronine sodium—
Mobile phaseand Chromatographic system— Proceed as directed in theAssay underLevothyroxine Sodium.
Standard solution— Use theStandard preparation prepared as directed in theAssay.
Test solution— Use theAssay preparation.
Procedure— Proceed as directed in theAssay underLevothyroxine Sodium.Calculate the quantity,in µg,of liothyronine sodium (C15H11I3NNaO4)in the portion of Tablets taken by the formula:
(672.96/650.98)(10C)(rU/rS),
in which 672.96and 650.98are the molecular weights of liothyronine sodium and liothyronine,respectively;Cis the concentration,in µg per mL,of USP Liothyronine RSin theStandard solution;andrUandrSare the liothyronine peak responses obtained from theTest solution and theStandard solution,respectively:not more than 2.0%of liothyronine is found.
Assay—
Mobile phase,Standard preparation,and Chromatographic system— Proceed as directed in theAssay underLevothyroxine Sodium.
Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 100µg of levothyroxine sodium,to a centrifuge tube,add 2glass beads,pipet 10mLofMobile phase into the tube,and mix on a vortex mixer for 3minutes.Centrifuge to obtain a clear supernatant,filtering if necessary.
Procedure— Proceed as directed in theAssay underLevothyroxine Sodium.Calculate the quantity,in µg,of levothyroxine sodium (C15H10I4NNaO4)in the portion of Tablets taken by the formula:
(798.85/776.87)(10C)(rU/rS),
in which 798.85and 776.87are the molecular weights of levothyroxine sodium and levothyroxine,respectively;Cis the concentration,in µg per mL,of USP Levothyroxine RSin theStandard preparation;andrUandrSare the levothyroxine peak responses obtained from theAssay preparation and theStandard preparation,respectively.
Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28–NF23Page 1128
Pharmacopeial Forum:Volume No.30(1)Page 120
Phone Number:1-301-816-8251