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Levothyroxine Sodium

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LevothyroxineSodium

C15H10I4NNaO4xH2O(anhydrous)
798.85

L-Tyrosine,O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-,monosodiumsalt,hydrate.
Monosodium L-thyroxinehydrate [25416-65-3].

Anhydrous [55-03-8].

LevothyroxineSodiumisthesodiumsaltofthelevoisomerofthyroxine,an
activephysiologicalprincipleobtainedfromthethyroidglandofdomesticated
animalsusedforfoodbymanorpreparedsynthetically.Itcontainsnotless
than97.0percentandnotmorethan103.0percentofC15H10I4NNaO4,
calculatedontheanhydrousbasis.
Packaging and storagePreserveintightcontainers,protectedfromlight.
USP Reference standards
USP Levothyroxine RS.
USP Liothyronine RS.

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Identification
A: Igniteabout50mginaplatinumdishoveraflame:itdecomposesandliberatesiodinevapors.
B: Toabout0.5mgadd7.5mLofacidsodiumchloridesolution(preparedbymixing300mLof
water,250mLofalcohol,100mLof1Nsodiumhydroxide,and100mLofhydrochloricacid)and
1mLofsodiumnitritesolution(1in100).Allowtostandinthedarkfor20minutes,andadd1.25
mLofammoniumhydroxide:apinkcolorisproduced.
Specific rotation

781S :between 5 and 6 .

Test solution:anamountequivalentto30mgofanhydrousLevothyroxineSodiumpermL,ina
mixtureofalcoholand1Nsodiumhydroxide(2:1).
Water, Method III

921 Dryabout500mg,accuratelyweighed,overphosphoruspentoxide

at60 andatapressurenotexceeding10mmofmercuryfor4hours:itlosesnotmorethan

11.0%ofitsweight.
Limit of inorganic iodides
Extracting solutionPreparea1in100solutionofsulfuricacidinwater.
Reference solutionDissolveanaccuratelyweighedquantityofpotassiumiodideinwaterto
obtainastocksolutioncontaining0.131mg,equivalentto0.100mgofiodidepermL.Transfer0.6
mLofthisstocksolutionintoa1000-mLvolumetricflask,dilutewiththe Extracting solutionto
volume,andmix.EachmLoftheReference solutioncontains0.06gofiodide.[ NOTEPrepare
thissolutiononthedayofuse.]
Test solutionTransfer7.5mgofLevothyroxineSodiumtoabeaker,add100mLofthe
Extracting solution,andsonicatefor5minutes.
Electrode systemUseaniodide-specific,ion-indicatingelectrodeandasilver-silverchloride
referenceelectrodeconnectedtoapHmetercapableofmeasuringpotentialswithaminimum
reproducibilityof1mV(seepH

791 ).

ProcedureTransfertheReference solutiontoabeakercontainingamagneticstirringbar.Rinse
anddrytheelectrodes,insertinthesolution,stirfor5minutesoruntilthereadingstabilizes,and
readthepotential,inmV.Repeatthisprocessusingthe Test solution.Therequirementsofthe
testaremetiftheTest solutionhasahigherpotential,inmV,thantheReference solution:thelimit
is0.08%.
Limit of liothyronine sodium
Mobile phase,andChromatographic systemProceedasdirectedintheAssay.
Standard solutionPrepareasdirectedforStandard preparation intheAssay.
Test solutionProceedasdirectedfortheAssay preparation.
ProcedureProceedasdirectedintheAssay.Calculatethequantity,ing,ofliothyronine
sodium(C 15H11I3NNaO4)inthesampletakenbytheformula:
(672.96/650.98)(10C)(r /r )
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inwhich672.96and650.98arethemolecularweightsofliothyroninesodiumandliothyronine,
respectively;Cistheconcentration,ingpermL,ofUSP Liothyronine RSintheStandard
preparation; andr andr aretheliothyroninepeakresponsesobtainedfromthe Test solutionand
theStandard solution, respectively:notmorethan2.0%ofliothyronineisfound.
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Assay
Mobile phasePrepareadegassedandfilteredmixtureofwaterandacetonitrile(60:40)that
contains0.5mLofphosphoricacidineach1000mL.Makeadjustmentsifnecessary(see System
Suitability underChromatography

621 ).

0.01 M Methanolic sodium hydroxideDissolve400mgofsodiumhydroxidein500mLofwater.


Cool,add500mLofmethanol,andmix.
Levothyroxine stock solutionDissolveanaccuratelyweighedquantityofUSP Levothyroxine RS
in0.01 M Methanolic sodium hydroxidetoobtainasolutionhavingaknownconcentrationofabout
0.4mgoflevothyroxinepermL.
Liothyronine stock solutionDissolveanaccuratelyweighedquantityofUSP Liothyronine RSin
0.01 M Methanolic sodium hydroxidetoobtainasolutionhavingaknownconcentrationofabout
0.4mgofliothyroninepermL.Makea1:100dilutionofthissolutionusing Mobile phase.
Standard preparationTransferappropriatevolumesofLevothyroxine stock solutionand
Liothyronine stock solutiontoasuitablecontainer,anddilutequantitativelyandstepwise,if
necessary,withMobile phasetoobtainasolutionhavingknownconcentrationsofabout10gof
levothyroxinepermLand0.2gofliothyroninepermL.
Assay preparationTransferanaccuratelyweighedportionofabout100gofLevothyroxine
Sodiumintoacentrifugetube,add2glassbeads,pipet10mLof Mobile phase intothetube,and
mixusingavortexmixerfor3minutes.Centrifugetoobtainaclearsupernatant,filteringif
necessary.
Chromatographic system(seeChromatography 621 )Theliquidchromatographisequipped
witha225-nmdetectoranda4.6-mm25-cmcolumnthatcontainspackingL10.Theflowrateis
about1.5mLperminute.Chromatographthe Standard preparation, andrecordthepeak
responsesasdirectedforProcedure: theresolution,R, betweenliothyronineandlevothyroxineis
notlessthan5.0;andtherelativestandarddeviationforreplicateinjectionsisnotmorethan2.0%
forlevothyroxine.
ProcedureSeparatelyinjectequalvolumes(about100L)ofthe Standard preparation andthe
Assay preparation intothechromatograph,recordthechromatograms,andmeasurethe
responsesforthemajorpeaks.Calculatethequantity,ing,ofC 15H10I4NNaO4intheportionof
LevothyroxineSodiumtakenbytheformula:
(798.85/776.87)(10C)(r /r )
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inwhich798.85and776.87arethemolecularweightsoflevothyroxinesodiumandlevothyroxine,
respectively;Cistheconcentration,ingpermL,ofUSP Levothyroxine RSintheStandard
preparation; andr andr arethelevothyroxinepeakresponsesobtainedfromthe Assay
preparation andtheStandard preparation, respectively.
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Auxiliary InformationStaff Liaison:ElenaGonikberg,Ph.D.,SeniorScientist


Expert Committee:(MDGRE05)MonographDevelopment-GastrointestinalRenalandEndocrine
USP30NF25Page2468