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PolyethyleneGlycol

Poly(oxy1,2ethanediyl), hydro hydroxy.

Polyethyleneglycol [25322683].

PolyethyleneGlycolisanadditionpolymerofethyleneoxideandwater,represented
bytheformula:
H(OCH2CH2)nOH

inwhichnrepresentstheaveragenumberofoxyethylenegroups.Theaverage
molecularweightisnotlessthan95.0percentandnotmorethan105.0percentofthe
labelednominalvalueifthelabelednominalvalueisbelow1000itisnotlessthan
90.0percentandnotmorethan110.0percentofthelabelednominalvalueifthe
labelednominalvalueisbetween1000and7000itisnotlessthan87.5percentand
notmorethan112.5percentofthelabelednominalvalueifthelabelednominalvalue
isabove7000.Itmaycontainasuitableantioxidant.
PackagingandstoragePreserveintightcontainers.

LabelingLabelittostate,aspartoftheofficialtitle,theaveragenominalmolecularweightofthe
PolyethyleneGlycol.Labelittoindicatethenameandquantityofanyaddedantioxidant.

CompletenessandcolorofsolutionAsolutionof5gofPolyethyleneGlycolin50mLofwateris
colorlessitisclearforliquidgradesandnotmorethanslightlyhazyforsolidgrades.

Viscosity 911 Determineitsviscosity,usingacapillaryviscosimetergivingaflowtimeofnotless

than200seconds,andaliquidbathmaintainedat98.90.3 C(210 F).Theviscosityiswithinthelimits
specifiedintheaccompanyingtable.ForaPolyethyleneGlycolnotlistedinthetable,calculatethelimitsby
interpolation.
Nominal Nominal
Average Viscosity Average Viscosity
Molecular Range, Molecular Range,
Weight Centistokes Weight Centistokes
200 3.9to4.8 2400 49to65
300 5.4to6.4 2500 51to70
400 6.8to8.0 2600 54to74
500 8.3to9.6 2700 57to78
600 9.9to11.3 2800 60to83
700 11.5to13.0 2900 64to88
800 12.5to14.5 3000 67to93
900 15.0to17.0 3250 73to105

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Nominal Nominal
Average Viscosity Average Viscosity
Molecular Range, Molecular Range,
Weight Centistokes Weight Centistokes
1000 16.0to19.0 3350 76to110
1100 18.0to22.0 3500 87to123
1200 20.0to24.5 3750 99to140
1300 22.0to27.5 4000 110to158
1400 24to30 4250 123to177
1450 25to32 4500 140to200
1500 26to33 4750 155to228
1600 28to36 5000 170to250
1700 31to39 5500 206to315
1800 33to42 6000 250to390
1900 35to45 6500 295to480
2000 38to49 7000 350to590
2100 40to53 7500 405to735
2200 43to56 8000 470to900
2300 46to60

Averagemolecularweight

PhthalicanhydridesolutionPlace49.0gofphthalicanhydrideintoanamberbottle,anddissolvein300
mLofpyridinefromafreshlyopenedbottleorthathasbeenfreshlydistilledoverphthalicanhydride.Shake
vigorouslyuntilcompletelydissolved.Add7gofimidazole,swirlcarefullytodissolve,andallowtostandfor
16hoursbeforeusing.

TestpreparationforliquidPolyethyleneGlycolsCarefullyintroduce25.0mLofthePhthalicanhydride
solutionintoadry,heatresistantpressurebottle.Addanaccuratelyweighedamountofthespecimen,
equivalenttoitsexpectedaveragemolecularweightdividedby160.Insertthestopperinthebottle,and
wrapitsecurelyinaclothbag.

TestpreparationforsolidPolyethyleneGlycolsCarefullyintroduce25.0mLofPhthalicanhydridesolution
intoadry,heatresistantpressurebottle.Addanaccuratelyweighedamountofthespecimen,equivalentto
itsexpectedmolecularweightdividedby160however,becauseoflimitedsolubility,donotusemorethan
25g.Add25mLofpyridine,fromafreshlyopenedbottleorthathasbeenfreshlydistilledoverphthalic
anhydride,swirltodissolve,insertthestopperinthebottle,andwrapitsecurelyinaclothbag.

ProcedureImmersethebottleinawaterbathmaintainedatatemperaturebetween96 and100 ,tothe

samedepthasthatofthemixtureinthebottle.Removethebottlesfromthebathafter5minutes,and,
withoutunwrapping,swirlfor30secondstohomogenize.Heatinthewaterbathfor30minutes(60minutes
forPolyethyleneGlycolshavingmolecularweightsof3000orhigher),thenremovefromthebath,andallow
ittocooltoroomtemperature.Uncapthebottlecarefullytoreleaseanypressure,removefromthebag,
add10mLofwater,andswirlthoroughly.Wait2minutes,add0.5mLofasolutionofphenolphthaleinin
pyridine(1in100),andtitratewith0.5NsodiumhydroxideVStothefirstpinkcolorthatpersistsfor15
seconds,recordingthevolume,inmL,of0.5NsodiumhydroxiderequiredasS.Performablank
determinationon25.0mLofPhthalicanhydridesolutionplusanyadditionalpyridineaddedtothebottle,and
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recordthevolume,inmL,of0.5NsodiumhydroxiderequiredasB.Calculatetheaveragemolecular
weightbytheformula:
[2000W]/[(BS)(N)]
inwhichWistheweight,ing,ofthePolyethyleneGlycoltakenfortheTestpreparation(BS)isthe
differencebetweenthevolumesof0.5Nsodiumhydroxideconsumedbytheblankandbythespecimen,
andNisthenormalityofthesodiumhydroxidesolution.

pH 791 :between4.5and7.5,determinedpotentiometrically,inasolutionpreparedbydissolving5.0g
ofPolyethyleneGlycolin100mLofcarbondioxidefreewaterandadding0.30mLofsaturatedpotassium
chloridesolution.

Residueonignition 281 :notmorethan0.1%,a25gspecimenandataredplatinumdishbeingused,

andtheresiduebeingmoistenedwith2mLofsulfuricacid.

Heavymetals 231 Mix4.0gwith5.0mLof0.1Nhydrochloricacid,anddilutewithwaterto25mL:

thelimitis5ppm.

Limitoffreeethyleneoxideand1,4dioxane

Strippedpolyethyleneglycol400Intoa5000mL3neck,roundbottomflaskequippedwithastirrer,a
gasdispersiontube,andavacuumoutlet,place3000gofPolyethyleneGlycol400.Atroomtemperature,
evacuatetheflaskcarefullytoapressureoflessthan1mmofmercury,applyingthevacuumslowlywhile
observingforexcessivefoamingduetoentrappedgases.Afteranyfoaminghassubsidedandwhile
stirringcontinuously,spargewithnitrogen,allowingthepressuretoriseto10mmofmercury.[NOTEThe
10mmvalueisaguideline.Deviationsfromthisvalueonlyaffectthetotaltimerequiredtostripthe
PolyethyleneGlycol400.]Continuestrippingforaminimumof1hour.[NOTECompletenessofthe
strippingprocedureshouldbeverifiedbymakingaheadspaceinjectionofthestrippedpolyethyleneglycol
400.]Shutoffthevacuumpump,andbringtheflaskpressurebacktoatmosphericpressurewhile
maintainingnitrogensparging.Removethegasdispersiontubewiththegasstillflowing,andthenturnoff
thegasflow.TransfertheStrippedpolyethyleneglycol400toasuitablenitrogenfilledcontainer.

Standardpreparation[CautionEthyleneoxideand1,4dioxanearetoxicandflammable.Preparethese
solutionsinawellventilatedfumehood.]Transfer4.90gofStrippedpolyethyleneglycol400toatared22
mLpressureheadspacevialthatcanbesealed.Add48Lof1,4dioxane,equivalentto50mgof1,4
dioxane,fromasyringe,seal,andcapthevial.Usingthespecialhandlingdescribedinthefollowing,
completethepreparation.Ethyleneoxideisagasatroomtemperature.Itisusuallystoredinalecturetype
gascylinderorsmallmetalpressurebomb.Chillthecylinderinarefrigeratorbeforeuse.Transferabout5
mLoftheliquidethyleneoxidetoa100mLbeakerchilledinwetice.Usingagastightsyringethathas
beenchilledinarefrigerator,transfer57Loftheliquidethyleneoxide,equivalentto50mgofethylene
oxide,tothemixturecontainedintheheadspacevial,andmix.Withtheaidofasyringe,transferabout2
mLofthissolutiontoa5mLbeaker.Transfer1.0mLofthissolutiontoa100mLvolumetricflask,dilute
withStrippedpolyethyleneglycol400tovolume,andmix.Transfer10mLofthissolutiontoa100mL
volumetricflask,dilutewithStrippedpolyethyleneglycol400tovolume,andmixtoobtainaStandard
preparationhavingknownconcentrationsof10gpergforbothethyleneoxideand1,4dioxane.Transfer
1.0mLoftheStandardpreparationtoa22mLpressureheadspacevial,sealwithasiliconeseptumwithor
withoutapressurereliefstarspringandapressurereliefsafetyaluminumsealingcap,andcrimpthecap
closedwithacapsealingtool.

ResolutionsolutionTransfer4.90gofStrippedpolyethyleneglycol400toa22mLpressureheadspace
vial.Pipet50Lofacetaldehydeintothevial.UsingthespecialhandlingdescribedunderStandard
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preparation,transferabout50.0Lofliquidethyleneoxideintothevial.Immediatelysealthevial,and
shake.Transfer1.0mLofthissolutiontoa100mLvolumetricflask,dilutewithStrippedpolyethylene
glycol400tovolume,andmix.Transfer10.0mLofthissolutiontoa100mLvolumetricflask,dilutewith
Strippedpolyethyleneglycol400tovolume,andmix.Transfer1.0mLofthisResolutionsolutiontoa22mL
pressureheadspacevialandseal,cap,andcrimpasdirectedfortheStandardpreparation.

TestpreparationTransfer1.0gofPolyethyleneGlycol,toa22mLpressureheadspacevialandseal,
cap,andcrimpasdirectedfortheStandardpreparation.

Chromatographicsystem(seeChromatography 621 )Thegaschromatographisequippedwitha

balancedpressureautomaticheadspacesamplerandaflameionizationdetectorandcontainsa0.32mm
50mfusedsilicacapillarycolumncontainingbondedphaseG27ina5mfilmthickness.Thecolumn
temperatureisprogrammedfrom70 to250 at10 perminute,withtheinjectionportat85 andthe
detectorat250 .Thecarriergasisheliumataflowrateofabout2.9mLperminute.Chromatographthe
Resolutionsolution,andrecordthepeakresponsesasdirectedforProcedure:therelativeretentiontimes
areabout0.9foracetaldehydeand1.0forethyleneoxideandtheresolution,R,betweentheacetaldehyde
peakandtheethyleneoxidepeakisnotlessthan1.3.

ProcedurePlacethevialscontainingtheStandardpreparationandtheTestpreparationintothe
automatedsampler,andheatthevialsatatemperatureof80 for30minutes.Usinga2mLgassyringe
preheatedinanovenat90 ,separatelyinject1.0mLoftheheadspacefromeachvialintothe
chromatograph,recordthechromatogram,andmeasuretheareasforthemajorpeaks.[NOTEA
headspaceapparatusthatautomaticallytransfersthemeasuredamountofheadspacemaybeusedto
performtheinjection.]Therelativeretentiontimesforethyleneoxideand1,4dioxaneareabout1.0and3.4,
respectively.Thepeakareasforethyleneoxideand1,4dioxaneinthechromatogramoftheTest
preparationarenotgreaterthanthoseofthecorrespondingpeaksinthechromatogramoftheStandard
preparation,correspondingtonotmorethan10gpergofethyleneoxideandnotmorethan10gpergof
1,4dioxane.

Limitofethyleneglycolanddiethyleneglycol(forPolyethyleneGlycolhavinganominalmolecular
weightlessthan450)

StandardpreparationPrepareanaqueoussolutioncontaining500geachofethyleneglycolandof
diethyleneglycolpermL.

TestpreparationTransferabout4gofPolyethyleneGlycol,accuratelyweighed,toa10mLvolumetric
flask,dissolveinanddilutewithwatertovolume,andmix.

Chromatographicsystem(seeChromatography 621 )Thegaschromatographisequippedwitha

flameionizationdetectoranda3mm1.5mstainlesssteelcolumnpackedwith12%G13onsupport
S1NS.Thecarriergasisnitrogenoranothersuitableinertgas,flowingatarateof50mLperminute.The
columntemperatureismaintainedatabout140 ,theinjectionporttemperatureismaintainedatabout250 ,
andtheflameionizationdetectortemperatureismaintainedat280 .

ProcedureInjectavolume(about2.0L)oftheStandardpreparationintothechromatograph,andrecord
thechromatogram,adjustingtheoperationalconditionstoobtainpeaksnotlessthan10cminheight.
Measuretheheightsofthefirst(ethyleneglycol)andsecond(diethyleneglycol)peaks,andrecordthe
valuesasP1andP2,respectively.Injectavolume(about2.0L)oftheTestpreparationintothe
chromatograph,andrecordthechromatogramunderthesameconditionsasthoseemployedforthe
Standardpreparation.Measuretheheightsofthefirst(ethyleneglycol)andsecond(diethyleneglycol)
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peaks,andrecordthevaluesasp1andp2,respectively.Calculatethepercentageofethyleneglycolinthe
portionofPolyethyleneGlycoltakenbytheformula:
(C1p1)/(P1W)

inwhichC1istheconcentration,ingpermL,ofethyleneglycolintheStandardpreparationandWisthe
weight,inmg,ofPolyethyleneGlycoltaken.Calculatethepercentageofdiethyleneglycolintheportionof
PolyethyleneGlycoltakenbytheformula:
(C2p2)/(P2W)

inwhichC2istheconcentration,ingpermL,ofdiethyleneglycolintheStandardpreparation:notmore
than0.25%ofthesumofethyleneglycolanddiethyleneglycolisfound.

Limitofethyleneglycolanddiethyleneglycol(forPolyethyleneGlycolhavinganominalmolecular
weight450orabovebutnotmorethan1000)

CericammoniumnitratesolutionDissolve6.25gofcericammoniumnitratein100mLof0.25Nnitric
acid.Usewithin3days.

StandardpreparationTransfer62.5mgofdiethyleneglycoltoa25mLvolumetricflask,dissolveina
mixtureofequalvolumesoffreshlydistilledacetonitrileandwater,dilutewiththesamemixturetovolume,
andmix.

TestpreparationDissolve50.0gofPolyethyleneGlycolin75mLofdiphenylether,previouslywarmed,if
necessary,justtomeltthecrystals,ina250mLdistillingflask.Slowlydistillatapressureof1mmto2mm
ofmercury,intoareceivergraduatedto100mLin1mLsubdivisions,until25mLofdistillatehasbeen
collected.Add20.0mLofwatertothedistillate,shakevigorously,andallowthelayerstoseparate.Coolin
anicebathtosolidifythediphenyletherandfacilitateitsremoval.Filtertheseparatedaqueouslayer,wash
thediphenyletherwith5.0mLoficecoldwater,passthewashingsthroughthefilter,andcollectthefiltrate
andwashingsina25mLvolumetricflask.Warmtoroomtemperature,dilutewithwatertovolume,if
necessary,andmix.Mixthissolutionwith25.0mLoffreshlydistilledacetonitrileinaglassstoppered,125
mLconicalflask.

ProcedureTransfer10.0mLeachoftheStandardpreparationandtheTestpreparationtoseparate50
mLflasks,eachcontaining15.0mLofCericammoniumnitratesolution,andmix.Within2to5minutes,
concomitantlydeterminetheabsorbancesofthesolutionsin1cmcellsatthewavelengthofmaximum
absorbanceatabout450nm,withasuitablespectrophotometer,usingablankconsistingofamixtureof
15.0mLofCericammoniumnitratesolutionand10.0mLofamixtureofequalvolumesoffreshlydistilled
acetonitrileandwater:theabsorbanceofthesolutionfromtheTestpreparationdoesnotexceedthatofthe
solutionfromtheStandardpreparation,correspondingtonotmorethan0.25%ofcombinedethyleneglycol
anddiethyleneglycol.

AuxiliaryInformationPleasecheckforyourquestionintheFAQsbeforecontactingUSP.
Topic/Question Contact ExpertCommittee
Monograph KevinT.Moore,Ph.D. (EM205)ExcipientMonographs2
Scientist
13018168369
USP32NF27Page1308
PharmacopeialForum:VolumeNo.31(3)Page897
ChromatographicColumn

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POLYETHYLENEGLYCOL

Chromatographiccolumnstextisnotderivedfrom,andnotpartof,USP32orNF27.

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