Document 7OERYBV5KVEnGKvzjbEGRQyNR
ARARGC - 1273 TELOMER RESEARCH PROGRAM
February 7, 2003 `DRAFTStud Plan:ImpurityAnalysisofArticles
pTrhoedufcotlslo(wsicngbeisloaw)p.ropSoasmepdlesstudwyillplbaen cfoolrleacntaeldysifsroomf pPiFlaOAplainnt 1f1acainliictlesesortrewaitledlbbeycotllloemcetre-dbafsreodm commercial manufacturing facies. Analyses need to be completed by May 2003 Tupss of Articles: representative Tentile, Corpet and Paper rile (11 total) pTrheesepnrto,paotsawlhaits dleesvielgsnenddofdineatlelyrmtihneecwohneftihdeenrcPeFoOfAthoissepreepseonrtiidnclaecvehlsa.tcTheiscosltluedcyt,eds, apnrdopfoistedi,sis Screening sud PROPOSED APPROACH
p-pAbn wLiCt/hMSr/elMaStimveetshtaonddoalrodgdyevwiilaltiboen uosfeldefsorthtahnes2e0%a,nalyses havinag lower limitof quantification of |
~The study will be conductedas a GLP study at acontract lab.
A preliminary extraction efficiencymethod validation study wil be conducted upfront
Preliminary Study Abe cporenldiumcitneadryormetthhroeedmvaatlriidcaetsi:oncfaorcpuese(dyloonne)n,supraipnegrhaantd etexxttrialceti(poonlyeefsftiecri)e.ncyExftarlalsctwiiotnhienff0ic-i1en1c0y%fowrill cach mairx will b determined at hee fortification levels sx replicates each):
ppb. 10 pb and 100 pb lSeavemlp.lesIpfiskciongutsinhgouexdpbeericmoenndtuscsthedowattahantaelxktarlaicnteiopnH,eftfoicrieednuciceeslcoasnsebseoafcPhFieOvAe,d erseapdeicliyalwyitahtinthhee1 7p0p-b T1h1e0%plaguniidel1i0neF,unth6escaomntprlaectseltasbawticlalcphroocfetehdewhiteh rsupnikiinnggaldedvietlonoanlesaacmhpdlaeysfots ontttwlSeofpa3rastaemapylse.s permats 11072saumnprlaetseodfcaarcpeetsbawiclklinbge,r5e4qusiarmepdlfeosrotfhitsepxotrteioannodft$h4eamsptuldeys(o5f4 psaamppel)es of unrated shaved carpe, The resus ofthis preliminary study wil be prepared a report, detailingthe method specifics including
SMatuerimalsmousfaemderthyod and results EReqaugiepnmtesntanudsesdandards sed APnraeplayrtaitciaolnPorfoscteodcukrsetsandard solution, preparation of fortification of aricles and preparation of calibration standards
= 35 o 32
32
S2 S55 2
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`TELOMER RESEARCH PROGRAM
Pprreepparroacteiosnsipnrgoocfesduarmepsles, sample fortification procedures, analyte extraction and final sample.
Instrumentation LCMS conditions LCIMS Calibration and Sampies Analysis
Calculation Methods
RDeetseuclttosrarnedspDonissec.ussion RCoenctorvoelriaensdor Blank ELxitmriatcotfioQnuaenfftiicfiiecnactyio(7)n and LiofmDetiecttion "Time required for analysis Special precautions
Conclusion
Article Analysis
EExxttrraaccttiioonneeffffiicciieennccyywfiolrl boethdeertearrtmiicnleesd:andor verified during sample analysis. Extraction aefnfailcyiseinscisees, wil be determined at | ppb, 10 ppb and 100 ppb. A control wil be included in the E(xhtirsamctaiyonchraecnogveedreipeesndwiilnlgbeupcoanrrrieesdulotustoafttehaecphoreflitmheinatrryeestluedvye)l.s: | ppb, 10 ppb and100ppb.
Sampling Procedure: Sthaempexltirnagctiisoancerfiftiicciaelnacsipesecatroefgaonoadl,yttihceanl tahnealsytsuidsytwhaitlisproofdteunceovreersluolotskewdi.thIhfidgohnceonrfigihdte,ncaen.d iSfee separate Sampling Procedure.
`Samples: Six samples analyzed for cach article, selectedusingblock design experiment.
`pSrOePpa(rsetdanadnadrdreovpieerwateidnbgypraoncaelydtuircea)l/pcrhoetmoicsotlryfoerxapnearltyssiasnodfpPosFsOibAlyionttheesrtsabrteifcolrees wacitluablework begins. Work should begin on samples by mid April 2003.
Background for Method Development
tEexmtprearcattiuorneiPnroccleodsucrde-:capMebtohtalneoulsi[nSguwgrgiesstt-atchtaitomnasthearkiearl,bfe eoxtrlactlbeydocweintwthriemfeutdgheanaotl3a00r0otopm]. Rpartoicoeodfure r4:1e, cmoetmhmaennodledoabrtyiccolnetrmaacsts.labC.lean-up and concentrate using solid phase extraction
Sample: 10grams Sample Number: 6
scuacbh-sfaomrpclasrpeftoamndcaccahrpaerttibcalecking,
2
grams
each
for
paper
and
textile
All prep done in plasic vals.
Sample should not be filtered unless particulates are observed.
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TELOMER RESEARCH PROGRAM
sIunptpelrineadl.SCtuarnrdeanrtldy:. hIentehtinksitnagndisartdo aisdodtosptiacnadlalrydefnriircheexdtraaccitdio(n.CF "CF"'COOHca)nbe
SSttoacnkdaStradndParredps:weighed into plastic vil and solubilized in HPLC grade methanol, CSeornicaelndtirlauttiioonnosfmsatdoeckinsMainldalr-dQ isWa1t0er0.0ppm (Img/mL) Prepare five standards in the range of 0.1 ppb (0 100 ppb - must bracket sample concentrations.
PSruegpgaerseteatdlseeaqsuefnoucrecfhorroamnaatloygsriasp:hic standards of PFOA to bracket the levels expected in the ofonreticfoinctartioolns(uanntdretahteedsaamnpdluensfotrotibfeieadnsaalmyzpelde.),Eoanceh csotnotrfolsasmapmlpeleanfoarltyizfieedd sahtotuhlediimnciloudfeqaut alnatst ttoatdieonmoannsdtroantcectohntarboalsselaimnpeleinftoerrtfiefrieedncaetihseemsatxhiamnu1m0l%evoefhloefqLuaOnQt.itation. The control i uscd
bAyaconsttraonldasrhdo.ulSdtbanedianrjdesctsehdouthlrdeehetinmebseainjtehcetebdeafgeir nevonefriyantcwgho atouttohmicaetesdamspelqeuse,nsaen,d ftohlelloawsted oinnjdeecrtioofninocfrtehaesisnegquceonncceentsrhaotuilodn.be sundard. Standards nd fortifications should be injected in
wfihthemceotnhcaennotlr.ation ofeither analyte in st of sample exceeds the rangeofthe standards, dilute
No data is availabe on the sabi of frozen samples
2W0h.e99n;uwshienrgetahseiLfitnheearReRsepgornessseiFoancMtoercMheothtohde cioseclmipclioeynetdo,ftdheterremlaitniavteiosnt,ansdqaurdardeevdi,atsihoonuolfdtbhee Sandards analyzed for the sample set mustbe less than 20%.
LCIMS conditions based upon submitted procedures:
PLrCodPuacrtamAenatleyrssis Method MInosbtirlumeenPth:asAeg:ilent 1100A: 50% 2mM* Ammonium Acetate 10% Methanol
B*:pr1e0fr0%thMatethheancaolncentration ofAA is bet. 10-20 mM
Gradient Profile
Time0 "2p0n
215 10200
is
2
E0l3owmU min 0033mmUmiinn 03mUmin
PInojsetctTiiomne:Vo2lummien: 2541 Analytical Column: Spher*ipsroerfberOsDhSorte2r.1coXlu2m0n0 miesmelStiuomn Pisacgkoiongd. Column Temperaure 40C
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TELOMER RESEARCH PROGRAM
MInasstrsumSepnet.c PMaircarmoemtaesrssQuattro Ultima lon Mode: Electrospray Negtive TSuounricneg P: aCraametperi2s 9lkaV:rCoyne 10 V; Hexapolel 0.2 volts; Aperture]0.0 vols; Source Block; "MTSemp.En1t5r0anCc;eD3e4sovollast,ioEnxiTte7m5p.vo2l5s0lCon Energy 0.6 volts; lon energy rap 0 MMSu2l.i:plifeorn 7en0e0rgvoylt1s.0 vol; lon energy ramp 0; LMResolution 13.3; HMResolution 13.1; Pressures Gas Call 9.0e5; Cone gas 2062 Li; Desolation Gas 77 Libr MMaRssMaSpfe4e1M3 R10M36(9multiple reaction motoring) (dels regarding similar approaches (0 the above ae available on request) Documentation Letter summarizing results will be acceptable for May 2003 deadline. Final report will be required
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