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PolyethyleneGlycol

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Poly(oxy­1,2­ethanediyl), ­hydro­ ­hydroxy­.
Poly(oxy­1,2­ethanediyl), ­hydro­ ­hydroxy­.
Poly(oxy­1,2­ethanediyl), ­hydro­ ­hydroxy­.

Poly(oxy­1,2­ethanediyl), ­hydro­ ­hydroxy­. Polyethyleneglycol [25322­68­3].

»PolyethyleneGlycolisanadditionpolymerofethyleneoxideandwater,represented

bytheformula:

H(OCH 2 CH 2 ) n OH

inwhichnrepresentstheaveragenumberofoxyethylenegroups.Theaverage

molecularweightisnotlessthan95.0percentandnotmorethan105.0percentofthe

labelednominalvalueifthelabelednominalvalueisbelow1000;itisnotlessthan

90.0percentandnotmorethan110.0percentofthelabelednominalvalueifthe

labelednominalvalueisbetween1000and7000;itisnotlessthan87.5percentand

notmorethan112.5percentofthelabelednominalvalueifthelabelednominalvalue

isabove7000.Itmaycontainasuitableantioxidant.

Packagingandstorage—Preserveintightcontainers.

Labeling—Labelittostate,aspartoftheofficialtitle,theaveragenominalmolecularweightofthe

PolyethyleneGlycol.Labelittoindicatethenameandquantityofanyaddedantioxidant.

Completenessandcolorofsolution—Asolutionof5gofPolyethyleneGlycolin50mLofwateris

colorless;itisclearforliquidgradesandnotmorethanslightlyhazyforsolidgrades.

Viscosity 911 —
Viscosity 911 —

Viscosity 911 Determineitsviscosity,usingacapillaryviscosimetergivingaflowtimeofnotless

than200seconds,andaliquidbathmaintainedat98.9±0.3 C(210
than200seconds,andaliquidbathmaintainedat98.9±0.3 C(210

than200seconds,andaliquidbathmaintainedat98.9±0.3 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—

Phthalicanhydridesolution—Place49.0gofphthalicanhydrideintoanamberbottle,anddissolvein300

mLofpyridinefromafreshlyopenedbottleorthathasbeenfreshlydistilledoverphthalicanhydride.Shake

vigorouslyuntilcompletelydissolved.Add7gofimidazole,swirlcarefullytodissolve,andallowtostandfor

16hoursbeforeusing.

TestpreparationforliquidPolyethyleneGlycols—Carefullyintroduce25.0mLofthePhthalicanhydride

solutionintoadry,heat­resistantpressurebottle.Addanaccuratelyweighedamountofthespecimen,

equivalenttoitsexpectedaveragemolecularweightdividedby160.Insertthestopperinthebottle,and

wrapitsecurelyinaclothbag.

TestpreparationforsolidPolyethyleneGlycols—Carefullyintroduce25.0mLofPhthalicanhydridesolution

intoadry,heat­resistantpressurebottle.Addanaccuratelyweighedamountofthespecimen,equivalentto

itsexpectedmolecularweightdividedby160;however,becauseoflimitedsolubility,donotusemorethan

25g.Add25mLofpyridine,fromafreshlyopenedbottleorthathasbeenfreshlydistilledoverphthalic

anhydride,swirltodissolve,insertthestopperinthebottle,andwrapitsecurelyinaclothbag.

Procedure—
Procedure—

Procedure—Immersethebottleinawaterbathmaintainedatatemperaturebetween96 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;(B–S)isthe

differencebetweenthevolumesof0.5Nsodiumhydroxideconsumedbytheblankandbythespecimen,

andNisthenormalityofthesodiumhydroxidesolution.

and N isthenormalityofthesodiumhydroxidesolution. pH 791 :
and N isthenormalityofthesodiumhydroxidesolution. pH 791 :

pH 791 :between4.5and7.5,determinedpotentiometrically,inasolutionpreparedbydissolving5.0g

ofPolyethyleneGlycolin100mLofcarbondioxide­freewaterandadding0.30mLofsaturatedpotassium

chloridesolution.

chloridesolution. Residueonignition 281 :
chloridesolution. Residueonignition 281 :

Residueonignition 281 :notmorethan0.1%,a25­gspecimenandataredplatinumdishbeingused,

andtheresiduebeingmoistenedwith2mLofsulfuricacid.

andtheresiduebeingmoistenedwith2mLofsulfuricacid. Heavymetals 231 —
andtheresiduebeingmoistenedwith2mLofsulfuricacid. Heavymetals 231 —

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

thelimitis5ppm.

Limitoffreeethyleneoxideand1,4­dioxane—

Strippedpolyethyleneglycol400—Intoa5000­mL3­neck,round­bottomflaskequippedwithastirrer,a

gasdispersiontube,andavacuumoutlet,place3000gofPolyethyleneGlycol400.Atroomtemperature,

evacuatetheflaskcarefullytoapressureoflessthan1mmofmercury,applyingthevacuumslowlywhile

observingforexcessivefoamingduetoentrappedgases.Afteranyfoaminghassubsidedandwhile

stirringcontinuously,spargewithnitrogen,allowingthepressuretoriseto10mmofmercury.[NOTE—The

10­mmvalueisaguideline.Deviationsfromthisvalueonlyaffectthetotaltimerequiredtostripthe

PolyethyleneGlycol400.]Continuestrippingforaminimumof1hour.[NOTE—Completenessofthe

strippingprocedureshouldbeverifiedbymakingaheadspaceinjectionofthestrippedpolyethyleneglycol

400.]Shutoffthevacuumpump,andbringtheflaskpressurebacktoatmosphericpressurewhile

maintainingnitrogensparging.Removethegasdispersiontubewiththegasstillflowing,andthenturnoff

thegasflow.TransfertheStrippedpolyethyleneglycol400toasuitablenitrogen­filledcontainer.

Standardpreparation—[Caution—Ethyleneoxideand1,4­dioxanearetoxicandflammable.Preparethese

solutionsinawell­ventilatedfumehood.]Transfer4.90gofStrippedpolyethyleneglycol400toatared22­

mLpressureheadspacevialthatcanbesealed.Add48µLof1,4­dioxane,equivalentto50mgof1,4­

dioxane,fromasyringe,seal,andcapthevial.Usingthespecialhandlingdescribedinthefollowing, completethepreparation.Ethyleneoxideisagasatroomtemperature.Itisusuallystoredinalecture­type

gascylinderorsmallmetalpressurebomb.Chillthecylinderinarefrigeratorbeforeuse.Transferabout5

mLoftheliquidethyleneoxidetoa100­mLbeakerchilledinwetice.Usingagas­tightsyringethathas

beenchilledinarefrigerator,transfer57µLoftheliquidethyleneoxide,equivalentto50mgofethylene

oxide,tothemixturecontainedintheheadspacevial,andmix.Withtheaidofasyringe,transferabout2

mLofthissolutiontoa5­mLbeaker.Transfer1.0mLofthissolutiontoa100­mLvolumetricflask,dilute

withStrippedpolyethyleneglycol400tovolume,andmix.Transfer10mLofthissolutiontoa100­mL

volumetricflask,dilutewithStrippedpolyethyleneglycol400tovolume,andmixtoobtainaStandard

preparationhavingknownconcentrationsof10µgpergforbothethyleneoxideand1,4­dioxane.Transfer

1.0mLoftheStandardpreparationtoa22­mLpressureheadspacevial,sealwithasiliconeseptumwithor

withoutapressurereliefstarspringandapressurereliefsafetyaluminumsealingcap,andcrimpthecap

closedwithacap­sealingtool.

Resolutionsolution—Transfer4.90gofStrippedpolyethyleneglycol400toa22­mLpressureheadspace

vial.Pipet50µLofacetaldehydeintothevial.UsingthespecialhandlingdescribedunderStandard

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preparation,transferabout50.0µLofliquidethyleneoxideintothevial.Immediatelysealthevial,and

shake.Transfer1.0mLofthissolutiontoa100­mLvolumetricflask,dilutewithStrippedpolyethylene

glycol400tovolume,andmix.Transfer10.0mLofthissolutiontoa100­mLvolumetricflask,dilutewith

Strippedpolyethyleneglycol400tovolume,andmix.Transfer1.0mLofthisResolutionsolutiontoa22­mL

pressureheadspacevial;andseal,cap,andcrimpasdirectedfortheStandardpreparation.

Testpreparation—Transfer1.0gofPolyethyleneGlycol,toa22­mLpressureheadspacevial;andseal,

cap,andcrimpasdirectedfortheStandardpreparation.

cap,andcrimpasdirectedforthe Standardpreparation. Chromatographicsystem (see Chromatography 621
cap,andcrimpasdirectedforthe Standardpreparation. Chromatographicsystem (see Chromatography 621

Chromatographicsystem(seeChromatography 621 )—Thegaschromatographisequippedwitha

balancedpressureautomaticheadspacesamplerandaflame­ionizationdetectorandcontainsa0.32­mm

×50­mfused­silicacapillarycolumncontainingbondedphaseG27ina5­µmfilmthickness.Thecolumn

temperatureisprogrammedfrom70 to250 at10
temperatureisprogrammedfrom70 to250 at10
temperatureisprogrammedfrom70 to250 at10
temperatureisprogrammedfrom70 to250 at10

temperatureisprogrammedfrom70 to250 at10 perminute,withtheinjectionportat85 andthe

to250 at10 perminute,withtheinjectionportat85 andthe

detectorat250.Thecarriergasisheliumataflowrateofabout2.9mLperminute.Chromatographthe

Resolutionsolution,andrecordthepeakresponsesasdirectedforProcedure:therelativeretentiontimes

areabout0.9foracetaldehydeand1.0forethyleneoxide;andtheresolution,R,betweentheacetaldehyde

peakandtheethyleneoxidepeakisnotlessthan1.3.

Procedure—PlacethevialscontainingtheStandardpreparationandtheTestpreparationintothe

Standardpreparation andthe Testpreparation intothe automatedsampler,andheatthevialsatatemperatureof80

automatedsampler,andheatthevialsatatemperatureof80 for30minutes.Usinga2­mLgassyringe

for30minutes.Usinga2­mLgassyringe

preheatedinanovenat90,separatelyinject1.0mLoftheheadspacefromeachvialintothe

chromatograph,recordthechromatogram,andmeasuretheareasforthemajorpeaks.[NOTE—A headspaceapparatusthatautomaticallytransfersthemeasuredamountofheadspacemaybeusedto

performtheinjection.]Therelativeretentiontimesforethyleneoxideand1,4­dioxaneareabout1.0and3.4,

respectively.Thepeakareasforethyleneoxideand1,4­dioxaneinthechromatogramoftheTest

preparationarenotgreaterthanthoseofthecorrespondingpeaksinthechromatogramoftheStandard

preparation,correspondingtonotmorethan10µgpergofethyleneoxideandnotmorethan10µgpergof

1,4­dioxane.

Limitofethyleneglycolanddiethyleneglycol(forPolyethyleneGlycolhavinganominalmolecular

weightlessthan450)—

Standardpreparation—Prepareanaqueoussolutioncontaining500µgeachofethyleneglycolandof

diethyleneglycolpermL.

Testpreparation—Transferabout4gofPolyethyleneGlycol,accuratelyweighed,toa10­mLvolumetric

flask,dissolveinanddilutewithwatertovolume,andmix.

flask,dissolveinanddilutewithwatertovolume,andmix. Chromatographicsystem (see Chromatography 621
flask,dissolveinanddilutewithwatertovolume,andmix. Chromatographicsystem (see Chromatography 621

Chromatographicsystem(seeChromatography 621 )—Thegaschromatographisequippedwitha

flame­ionizationdetectoranda3­mm×1.5­mstainlesssteelcolumnpackedwith12%G13onsupport

S1NS.Thecarriergasisnitrogenoranothersuitableinertgas,flowingatarateof50mLperminute.The

columntemperatureismaintainedatabout140,theinjectionporttemperatureismaintainedatabout250,

andtheflame­ionizationdetectortemperatureismaintainedat280.

andtheflame­ionizationdetectortemperatureismaintainedat280.

Procedure—Injectavolume(about2.0µL)oftheStandardpreparationintothechromatograph,andrecord

thechromatogram,adjustingtheoperationalconditionstoobtainpeaksnotlessthan10cminheight.

Measuretheheightsofthefirst(ethyleneglycol)andsecond(diethyleneglycol)peaks,andrecordthe valuesasP 1 andP 2 ,respectively.Injectavolume(about2.0µL)oftheTestpreparationintothe

chromatograph,andrecordthechromatogramunderthesameconditionsasthoseemployedforthe

Standardpreparation.Measuretheheightsofthefirst(ethyleneglycol)andsecond(diethyleneglycol)

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peaks,andrecordthevaluesasp 1 andp 2 ,respectively.Calculatethepercentageofethyleneglycolinthe

portionofPolyethyleneGlycoltakenbytheformula:

(C 1 p 1 )/(P 1 W)

inwhichC 1 istheconcentration,inµgpermL,ofethyleneglycolintheStandardpreparation;andWisthe

weight,inmg,ofPolyethyleneGlycoltaken.Calculatethepercentageofdiethyleneglycolintheportionof

PolyethyleneGlycoltakenbytheformula:

(C 2 p 2 )/(P 2 W)

inwhichC 2 istheconcentration,inµgpermL,ofdiethyleneglycolintheStandardpreparation:notmore

than0.25%ofthesumofethyleneglycolanddiethyleneglycolisfound.

Limitofethyleneglycolanddiethyleneglycol(forPolyethyleneGlycolhavinganominalmolecular

weight450orabovebutnotmorethan1000)—

Cericammoniumnitratesolution—Dissolve6.25gofcericammoniumnitratein100mLof0.25Nnitric

acid.Usewithin3days.

Standardpreparation—Transfer62.5mgofdiethyleneglycoltoa25­mLvolumetricflask,dissolveina

mixtureofequalvolumesoffreshlydistilledacetonitrileandwater,dilutewiththesamemixturetovolume,

andmix.

Testpreparation—Dissolve50.0gofPolyethyleneGlycolin75mLofdiphenylether,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.

Procedure—Transfer10.0mLeachoftheStandardpreparationandtheTestpreparationtoseparate50­

mLflasks,eachcontaining15.0mLofCericammoniumnitratesolution,andmix.Within2to5minutes,

concomitantlydeterminetheabsorbancesofthesolutionsin1­cmcellsatthewavelengthofmaximum

absorbanceatabout450nm,withasuitablespectrophotometer,usingablankconsistingofamixtureof

15.0mLofCericammoniumnitratesolutionand10.0mLofamixtureofequalvolumesoffreshlydistilled

acetonitrileandwater:theabsorbanceofthesolutionfromtheTestpreparationdoesnotexceedthatofthe

solutionfromtheStandardpreparation,correspondingtonotmorethan0.25%ofcombinedethyleneglycol

anddiethyleneglycol.

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ChromatographicColumn—

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Chromatographiccolumnstextisnotderivedfrom,andnotpartof,USP32orNF27.