Levothyroxine Sodium Tablets

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LevothyroxineSodiumTablets

LevothyroxineSodiumTabletscontainnotlessthan90.0percentandnot
morethan110.0percentofthelabeledamountoflevothyroxinesodium
(C15H10I4NNaO4).
Packaging and storagePreserveintight,light-resistantcontainers.
LabelingWhenmorethanone Dissolution testisgiven,thelabelingstatesthe Dissolution test
usedonlyif Test 1 isnotused.
USP Reference standards
USP Levothyroxine RS.
USP Liothyronine RS.

11

Identification
Solvent systemMix5volumesoftert-amylalcohol,4volumesofwater,and1volumeof
ammoniumhydroxide,shake,andallowtostand.Transfertheupperphasetoasuitable
chromatographicchamberarrangedforthin-layerchromatography,pouringitoverthepaper
lining,coverthechamber,andallowtostandfor1hour.
Detection reagentAdd65mLof2Nhydrochloricacidto50mLofa1in10solutionofsodium
arsenitein1Nsodiumhydroxide,withvigorousstirring.Mix1volumeofthissolutionwith5
volumesofa27in1000solutionofferricchloridein2Nhydrochloricacidand5volumesof
freshlypreparedpotassiumferricyanidesolution(35in1000).
Standard solutionPrepareasolutionofabout15mgofUSP Levothyroxine RS,accurately
weighed,in100mLofamixtureof19volumesofmethanoland1volumeofammonium
hydroxide.Dilute10.0mLofthissolutionwiththesamesolventto50.0mL,andmix.
Test solutionShakeanamountofpowderedTablets,equivalenttoabout60goflevothyroxine
sodium,with2mLofamixtureof19volumesofmethanoland1volumeofammoniumhydroxide
inacentrifugetubefor10minutes,andcentrifuge.
ProcedureApply10-Lvolumesofthe Test solution andofthe Standard solution,respectively,
toathin-layerchromatographicplatecoatedwitha0.1-mmlayerofcellulose.Developtheplatein
the Solvent system untilthesolventfronthasmovednotlessthan10cmbeyondthepointof
applicationofthe Test solution,air-dry,andspraytheplatewith Detection reagent: the
chromatogramofthe Test solution showsabluespotcorrespondingin R valuetothe
chromatogramfromthelevothyroxine Standard solution.
F

Dissolution

711 [NOTEAllcontainersthatareincontactwithsolutionscontaining

levothyroxinesodiumaretobemadeofglass.]
TEST1

Medium: 0.01Nhydrochloricacidcontaining0.2%sodiumlaurylsulfate;500mL.
Apparatus 2: 50rpm.
Time: 45minutes.
DeterminetheamountofC 15H10I4NNaO4dissolvedbyemployingthefollowingmethod.
Mobile phasePrepareafilteredanddegassedmixtureofmethanoland0.1%phosphoricacid
(60:40).Makeadjustmentsifnecessary(seeSystem Suitability underChromatography

621 ).

Standard solutionPrepareastocksolutionofUSP Levothyroxine RSinmethanolhavinga

knownconcentrationofabout0.1mgpermL.Dilutethisstocksolutionwith Medium toobtaina
solutionhavingaconcentrationsimilartothatexpectedinthe Test solution.
Test solution[NOTEPriortouse,checkthefiltersforabsorptivelossofdrug.]Useafiltered
portionofthesolutionundertest.
Chromatographic system(seeChromatography 621 )Theliquidchromatographisequipped
witha225-nmdetectoranda4.6-mm25-cmcolumnthatcontainspackingL1.Theflowrateis
about2mLperminute.Chromatographthe Standard solution, andrecordthepeakresponsesas
directedfor Procedure: thetailingfactorisnotmorethan1.5;andtherelativestandarddeviationis
notmorethan4.0%.
ProcedureSeparatelyinjectequalvolumes(about800L)ofthe Standard solution andthe Test
solution intothechromatograph,recordthechromatograms,andmeasuretheresponsesforthe
majorpeaks.CalculatetheamountofC 15H10I4NNaO4dissolved.
TolerancesNotlessthan70%(Q) ofthelabeledamountofC 15H10I4NNaO4isdissolvedin45
minutes.
TEST2Iftheproductcomplieswiththistest,thelabelingindicatesthatitmeetsUSP Dissolution

Test 2.
Medium, Apparatus, Mobile phase, Standard solution, Test solution, Chromatographic system,
andProcedureProceedasdirectedfor Test 1.
Time: 15minutes.
TolerancesNotlessthan80% (Q) ofthelabeledamountofC 15H10I4NNaO4isdissolvedin15
minutes.
TEST3Iftheproductcomplieswiththistest,thelabelingindicatesthatitmeetsUSP Dissolution

Test 3.
Medium, Apparatus, Time, Standard solution, andTest solutionProceedasdirectedforTest 1.

[NOTEFiltertheStandard solution inamanneridenticaltotheTest solution.]

DeterminetheamountofC 15H10I4NNaO4dissolvedbyemployingthefollowingmethod.
Mobile phasePrepareafilteredanddegassedmixtureofwaterandacetonitrile(65:35)with0.5
mLofphosphoricacidperL.Makeadjustmentsifnecessary(see System Suitabilityunder
Chromatography

621 ).

Chromatographic system (see Chromatography 621 )Theliquidchromatographisequipped

witha225-nmdetectoranda4.6-mm25-cmcolumnthatcontains5-mpackingL10.The
columntemperatureismaintainedat30 .Theflowrateisabout1.5mLperminute.
ChromatographtheStandard solution, andrecordthepeakresponsesasdirectedfor Procedure:
thetailingfactorisnotmorethan1.5;andtherelativestandarddeviationisnotmorethan4.0%.
ProcedureSeparatelyinjectequalvolumes(about100L)ofthe Standard solutionandthe
Test solution intothechromatograph,recordthechromatograms,andmeasuretheresponsesfor
themajorpeaks.CalculatetheamountofC 15H10I4NNaO4.
TolerancesNotlessthan80%(Q) ofthelabeledamountofC 15H10I4NNaO4isdissolvedin45
minutes.
TEST4Iftheproductcomplieswiththistest,thelabelingindicatesthatitmeetsUSP Dissolution

Test 4.
NOTEDonotusepaddlestirrerswithsyntheticcoating.

Medium: 0.01Nhydrochloricacid;500mLfortabletslabeledtocontainbetween25gand175
goflevothyroxinesodium;900mLfortabletslabeledtocontain200gor300gof
levothyroxinesodium.
Apparatus 2: 75rpm.
Time: 45minutes.
DeterminetheamountofC 15H10I4NNaO4dissolvedbyemployingthefollowingmethod.
Mobile phasePrepareafilteredanddegassedmixtureofwater,acetonitrile,and85%
orthophosphoricacid(700:500:2).Makeadjustmentsifnecessary(see System Suitabilityunder
Chromatography

621 ).

Standard solutionPrepareastocksolutionbytransferringabout100mgof USP Levothyroxine

RS,accuratelyweighed,toa100-mLvolumetricflask.Add80mLofalcoholand1mLof1N
hydrochloricacid,sonicateforabout2minutes,dilutewithalcoholtovolume,andmix.Dilutethis
stocksolutionwithamixtureofalcoholandwater(1:1)toobtainasolutionhavingaconcentration
of0.01mgoflevothyroxinepermL.Dilutethisintermediatesolutionwith Mediumtoobtaina
solutionhavingaconcentrationsimilartothatexpectedinthe Test solution.

Test solutionUseacentrifugedportionofthesolutionundertest.
Chromatographic system (see Chromatography 621 )Theliquidchromatographisequipped
witha225-nmdetectoranda4.0-mm12.5-cmcolumnthatcontainspackingL7.Theflowrateis
about1.5mLperminute.Chromatographthe Standard solution, andrecordthepeakresponses
asdirectedforProcedure:thetailingfactorisnotmorethan1.5;andtherelativestandard
deviationisnotmorethan4.0%.
ProcedureSeparatelyinjectequalvolumes(about500L)ofthe Standard solutionandthe
Test solution intothechromatograph,recordthechromatograms,andmeasuretheresponsesfor
themajorpeaks.CalculatetheamountofC 15H10I4NNaO4.
TolerancesNotlessthan80%(Q) ofthelabeledamountofC 15H10I4NNaO4isdissolvedin45
minutes.
Uniformity of dosage units

905 : meettherequirements.

Limit of liothyronine sodium

Mobile phaseandChromatographic systemProceedasdirectedinthe Assay under
Levothyroxine Sodium.
Standard solutionUsethe Standard preparation,preparedasdirectedinthe Assay.
Test solutionUsethe Assay preparation.
ProcedureProceedasdirectedinthe Assay under Levothyroxine Sodium.Calculatethe
percentageofliothyroninesodium(C 15H11I3NNaO4)intheportionofTabletstakenbytheformula:
(672.96/650.98)(1000C/W)(r /r )
U

inwhich672.96and650.98arethemolecularweightsofliothyroninesodiumandliothyronine,
respectively; Cistheconcentration,ingpermL,ofUSP Liothyronine RSinthe Standard
solution; Wistheamount,ing,oflevothyroxinesodiumintheportionofTablets,basedonthe
labelclaim,takentopreparetheTest solution;and r and r aretheliothyroninepeakresponses
obtainedfromthe Test solution andthe Standard solution, respectively:notmorethan2.0%of
liothyronineisfound.
U

Assay
Mobile phase, Standard preparation,andChromatographic systemProceedasdirectedinthe
Assay under Levothyroxine Sodium.
Assay preparationWeighandfinelypowdernotfewerthan20Tablets.Transferanaccurately
weighedportionofthepowder,equivalenttoabout100goflevothyroxinesodium,toacentrifuge
tube,add2glassbeads,pipet10mLof Mobile phase intothetube,andmixonavortexmixerfor
3minutes.Centrifugetoobtainaclearsupernatant,filteringifnecessary.

ProcedureProceedasdirectedinthe Assay under Levothyroxine Sodium.Calculatethe

quantity,ing,oflevothyroxinesodium(C 15H10I4NNaO4)intheportionofTabletstakenbythe
formula:
(798.85/776.87)(10C)(r /r )
U

inwhich798.85and776.87arethemolecularweightsoflevothyroxinesodiumandlevothyroxine,
respectively; C istheconcentration,ingpermL,ofUSP Levothyroxine RSinthe Standard
preparation; and r and r arethelevothyroxinepeakresponsesobtainedfromthe Assay
preparation andthe Standard preparation, respectively.
U

Auxiliary InformationStaff Liaison:ElenaGonikberg,Ph.D.,SeniorScientist

Expert Committee:(MDGRE05)MonographDevelopment-GastrointestinalRenalandEndocrine
USP30NF25Page2470
Pharmacopeial Forum:VolumeNo.31(2)Page413
Phone Number:1-301-816-8251