Transcript
Page 1: Drug delivery related to metabolites in human breath – fi ... · Drug delivery related to metabolites in human breath – fi rst results of long term clinical studies using MCC/IMS

Drug delivery related to metabolites in human breath – fi rst results of long term clinical studies using MCC/IMS

* Korea Ins tute of Science and Technology Europe Forschungsgesellscha mbH (KIST Europe)Campus E 7 1 - 66123 Saarbrücken - Germany

phone + 49 (0) 681 9382 229 - fax + 49 (0) 681 9382 240

h p://www.kist-europe/r_cd_jibb.htmlh p://www.kist-europe.comh p://www.kist-europe.de

Contact: PD Dr. Jörg Ingo Baumbach Head of Department Microfl uidics and Clinical Diagnos cs [email protected]

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Part of a IMS-Chromatogram of human breath

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h p:h p:h p:h p:h p:h phh p:h p:h p:p:h p:h p:p:ph p:p:h p:h p:h p:h p phh p //www//ww//www//www//www/www//www//wwwwwwwww//www//www//www//www//www//www/wwww//www////www//www//www/ wwww// .kist.kist.kis.kis.kist.kist.kist.kist.kis.kis.kist.kis.kisis.kist.kisi.ki.kis.kisss.kiskis.kisi -euro-e-euro-euro-euroeuroeuroeuroeuroeuroeuroeuroeuroeuroeurouroeureuro--euroe pe/r_pe/rpe/r_pe/r_pe/r_pe/r_pe/rpe/r_e/re/r_pe/r_e/re/repe/r_pe/r_pe/r_/pe/rpe/rpe/r_pe/r_pe/p rp rpe/ cd_jicd_jicd_jicd_jicd_jidcd_jicd_jicd_jicd_jiccd jicd_cd_jicd_jid_jicd_ id_jijijic _jiiijibb.htbb.htbb.htbb.htbb.htbb.htbb.bbbb.bb.hbb.hbb.bb.bb.ht.hthtbb.htbb.bbb ..hhb h mmmmlmlmlmlmlmlmlmlmlmlmmlmmlmmhhhhhhhh ///////////////////// kkkkkkk

ContaContaContaContaContaonontaContaontontontContaontContaonContaContaContaContaoonttnoo ct:ct:ct:ct:ctcctct:ct:ct:tct PDPDPDPDPDPDPDDPDDPDDPDPDPDPPDPPDDDP Dr JDr. JDr. JDrDr.Drr. Jr Jr. JJJJDr. JDDr.r. JDr. JJrD JDD örg Iörg Iörg Iörg Iörg örgörg Iörg örg Iörg Iörg Iörg Iörg Iörg Iörg örg örg Irg Irgg örg Iörg Iör ngo Bngo Bngo Bgo Bgoggo Bgo Bgo Bngo Bngo Bgo Bgo Bgo Bgo Bgo Boo Bgo Bgo Bgo Bngo gogo Bngo Bgo ngo on aumaumbaaumbaaumbaaumbaaumbaaumbaaumbaumbauaumbaumbaaumbaaumbaumbaumaumbambaumbaaumbaaumbbauaumbmbaumbmbaaa bu am chchchchcchchchchchcchccchchchhddddd fff flflflflfl dddddddddd ddd lll lll

* Kor* Kor* Kor* Ko* Kor* Kor* Kor* Kor* Kor* Kor* Kor* Kor* Kor** Kor* Kor* Kor* K* KKKKKooororeaea Inea Inea Inea Inea Inea Inea Inea Inea Inea Inea Ina Ina Inea Ineea Ineaeaea InInnns tus tus tus tus tus tus tus tus tus tus tus tus tuts tus tss tss ttuttute ofte ofte ofte ofte ofe ofte ofte ofte ofe ofte ofe ofe ofte oe ofte ofte ofte ofe oeeee ooff ScieScieScieScieS iS iScieScieScieScieScieS iScieScieScieScieScieScieSScieSciec nce ancence ancnce ance ance ance ance ance ance ancecnce annce aceceeee nd Tend Tend Tend Tend Tend Tend Ted TTend Tend Tend Tend Tend Tend Tend Tend Teddd Td echnolchnolchnochnolchnolchnohnochnolnohnchnolnochnolchnchnnochnolhnononoccchnolchnolchnohnohnolnooooooology Eogy Eogy Eogy Eogy Eogy Eogy Eogy Egy Eogy Egy Eogy EEogyogy Eogy Eogy Eogogy EEuropeurouropeuropeuropeuropeurouropeurourourouroopepepepeuro epruurouropeurourorooopppepepeppepee ForsForsForsForsForsForsFororForsForsorsForsForsorsorsForsForsForsForsorsoroorsorsorsr chungchunchungchungchungchungchunchunghungchungchunchungggchunghungchuchungchungchunghhuunuunggsgessgessgessgesesgesesgesegesegesegesegesegesegesggesgessesg ses seeeessgesgsgesgegesegesgeseeseseseellschllscllsclschllschllschllscllsclschllschchchchllsllschllschllschchchclllschlsscscschhhhhha ma ma ma ma maa mma ma mmma ma ma mmmma ma ma ma mmbH (KbH (KbH (KbH (KbH (KHH (H (KH (H (KbH (KbH (KHH (H (KKH (bH (KbH (KH (H (bH (KHH ((bH (KbH (KH (HH (HHH (KKIST EIST EIST EST EST ET ET ET ET EET EET ET ET ETT EIST ET EEIST EIST ESTTTT ET Europeuropeuropeuropeuropeuroperopeuropeuropeepepeperopeeeuropeuroperoperoperooopee)))))))))))) h p:h p:h p:h ph p:h ph p:h p:hh p:h p:h p:p:h p:hh ph phhhhh ph phhh ppppppp:://www//www//ww//www//www//www//www//wwwwww/www//www//www//www//www//www//ww//www//www//wwwww////ww//w//w//w//w//wwwwwwwwwwwww kistkistkiskistkistkistkistkistkiskiskiskiiskiskistkiskiskisikiskiskikikkistkistkkkistkistkistisisstt eeuroeuroeuroeuroeuroeuroeuroeuroeuroueuroeuroeurouroeuroeeeeeuroeeeuroeeurouururourourope/rpe/rpe/rpe/rpe/rpe/rpe/rpe/rpe/re/re/re/pe/r/rpe/rpe/rpe/rpe/re/r//re/reeee/repppe/rpepe/rpe/rpe/re/re/re/ree/e/r//rr cdcdcdddcdd jcd jid jd jid jicd jicd jicd jicd jicddd jdcdcdddccdccd jcd jid jidd jiibb htbb htbb htbb htbb htbb htbb htbbb htbb htbb htb htbb htbbbb htbb htbb htbb htb hbb htb htbbb htb htbb htbbbbb hbbbbbb hthhttmmmmmmmmmlmlmlmlmlmlmlmmmmmlmmmmmmmlmmmmmlmlml ContaContaContaContaContContaContaContaContaContaontontaontatantaContaataContaontaontaContaoono tContaContaContaContontontaoontontontontaacct:ct:ct:ct:ct:ct:ct:ctcct::cctct:ct: PDPDPDPDDDDDDPDPPDDDPDPDDPDPDPDPDPPDDDDDDDD Dr JDr JDr JDr JDr JDr JrDrDr JDr JDr JrDrD Jr JDr Jr JrDDDr JDDDrDrrr JJJJörg Iörg Iörg Iöörg Iörg Iörg Iörg Iörg Iörgörgörgörg Iörg Iörgörg Iörg Iörg Iörgörg Iörg Iörgöörg Iörgörg Iööörgörgörg Iörgrg Irgrgg Ingo Bngo Bngo Bngo Bgo Bgo Bgo Bngo Bgogo Bo Bngo Bgo Bgo BBgo Bgo Bgo Bgo BBo Bngo Bnngo Bgo Bgo Bgo Bgo Bgo Bgogo Boo BBaumbaaumbaaumbaaumbaumbaaumbaaumbaaumbaaumbaumbaaumbaumbaumbaaumbaaumbaumbabaumbaaaumbaaumbaaumbaaumbaaumaaauaaaumaumbaumbaumbaumbaumbauumbmmbb hhhchchcchchchchchchchchhhchchhchcccccchchchch

M. Westhoff 1, P. Li erst1, S. Maddula2, J.I. Baumbach2,3

1 Lung Clinic Hemer, Theo-Funccius-Str. 1, 58675 Hemer, Germany2 KIST Europe, Department Microfl uidics and Clinical Diagnos cs, Campus E 71, 66123 Saarbrücken, Germany

3 B&S Analy k, BioMedicalCenter Dortmund, O o-Hahn-Str. 15, 44227 Dortmund, Germany

Acknowledgements

The fi nancial support of the Ministry of Educa on, Science and Technology (MEST) of the Republic

Korea is acknowledged thankfully. Part of the work on this paper has been supported by Deutsche For-schungsgemeinscha (DFG) within the Collabora -ve Research Center (Sonderforschungsbereich) SFB 876 „Providing Informa on by Resource-Constrai-ned Analysis“, project TB1 “Resource-Constrained

Analysis of Spectrometry Data“.

In addi on, the work was supported partly by the German Federal Ministry of Economics and Tech-

nology based on a decision of the German Bundes-tag within the project KF2368102AKO.

The experimental work described was carried out partly at ISAS Dortmund, Germany.

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0 62 124 186 248

0,002

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0,014

0,016

GAG

GA

G /

a.u.

IMS - Peak height

Sig

nal h

eigh

t / a

.u.

Time / d

Hunter Disease

Peak P-77.2/0.601

IMS

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The fiThe fiThe fiThe fiThe fiThe fiThe fiThe fiThe fiThe fiThe fiThe fiThe fiThe fififihe financnancnancnancnancnancnancnancnancnancnancnancnancancn ial sial sial sial sial sial sial sial sial sial sial sial sial sial sial sl supporupporupporupporupporupporupporupporupporuppoupporupporupporupporup t oft of t of t oft oft of t of t of t of t of t oft oft oft of of the Mthe Mthe Mthe Mthe Mthe Mthe Mthe Mthe Mthe Mthe Mthethe Me Mthe Ministinistinistinistinistinistinistnistinistinistnistinisti tinistnististry ofry ofry ofry ofry ofry ofry ofry ofry ofry ofry ofry ofry ofry ofry of EducEducEducEducEducEducEducEducEducEdEducEducEducEdEdd a ona ona ona ona ona ona ona onna ona oa ona on,,,,,,,,ScienScienScienSciScScienScienScienScienScienScieScienScScieSccc ce ance ance ance ance ance ance ance ance ance ance ance ance ance anc d Tecd Tecd Tecd Tecd Tecd Tecd Tecd Tecd Ted Td Ted Tecd Tecd TecTe hnolohnolohnolohnolohnolohnolohnolohnolohnolohnolohnolohnolohnoloology (Mgy (Mgy (Mgy (Mgy (Mgy (Mgy (Mgy (Mgy (Mgy (Mgy (Mgy (Mgy (M(Mgy (MEST)EST)EST)EST)EST)EST)EST)EST)EST)EST)EST)EST)ST)ESTEST) of thof thof thof tof thof thof thof thof thof thof thof thof thof thof the Repe Repe Repe Repe Repe Repe Repe Repe Ree Repe Repe Ree Repe Ree RepRee ublicublicublicublicubublicublicublicubliublicubuuub

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nolognolognolognononolognolognolognolognolognolognonolognolognolognonolognonolognolognon y basy basy bay basy basy basy basy basy basby basy basy basy basy basy basy basy basy basbby basy basy basbasasy basy babbb seedededed oned ond ond ond ond ond ond oned ond od onddd oned oned odee ne a dea dea dea dea dea dea dea dea dea dea dea dea dea dedecisicisiocisiocisicisiocisiciscisicisicisicisiioioiooiocisicisiioc ooion ofn on ofn ofn ofn of n on of of ofn of n of n of n of ofn of n ofn offn ofofn ofn on oof the Gthethe Ghe Ghe Ghe Ghe Ghe Ghe Ghe Ghe GGhe Ghe Ge Ghhe Ge Ge GGthh Gtttt ermanermanermanermanermanermanermanermanermanermanermanermanermanrmaermane BBBundBBundBundBundundBundBundBundBundBundBundBundundBundBunuBB es-es-es-es-es-es-es-es-es-es-es-es-es-ss-tag wtag wtag wtag wtag wtag wtag wtag wtag wtag wtag wtag wtag wtag wtag wtag wtag wtag wtag wagtag wtag wgag wwgg wt ititththinithithinthinthinthinthinhinthinthinthinthinthinithinnttitthiniti the the the the the the thehethethethe hthethe the thee projeprojeprojeprojeprojeprojeprojeprojeprojeprojeejeeeojeprojeprojeojeeprojejeeecccct KFct KFct KFct KFct Kct KFt KFct KFct KFct KFct KFctt KFKFct KFct KF236812368123681236812368123681368123683683681236823682366812368123682368236823682368236812368 02AKO02AKO02AKO02AKO02AKO02AKO02AKO2AKOAKO02AKO02AKO02AKO02AKO02AKO02AKO00000 ....

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G /

a.u

d

The concentra ons were higher than the concentra ons of

all pa ents ever tested with MCC/IMS. Furthermore, a peak P-77.2/0.601 was found,

which decreased a er few weeks of therapy and needs further biochemical characterisa on.

Parallel GC/MSD inves ga ons suggest (S)-(+)-6-Methyl-1-octanol[110453-78-6], Cyclohexanone, 5-methyl-2-(1-methylethyl)- [10458-14-7], Benzaldehyde, 2,5-dimethyl-

[5779-94-2], Ethanone, 1-(4-methylphenyl)- [122-00-9], Dodecane [112-40-3] or Decanal [112-31-2].

These preliminary data show that breath analysis in pa ents with metabolic disorders might give

further informa on about metabolism, especially under enzyme replace-

ment therapy.

Pa ent Father Mother

GAG

PartPartPartPartPartartr

PPa ePa ePa ePa ePa eeeentntntntnnn

Hunter disease is a mucopolysaccharidosis for

which enzyme replacement therapy with idursulfase has been off ered for 3 ye-

ars. Therapy can be monitored by the urinary concentra on of dermatan sulfate and heparin sul-fate. A 38-year-old male person suff ering from Hun-ter disease has been treated with idursulfase for a year, showing drama c clinical improvement. Addi onally,

the pa ent had breath analysis using MCC/IMS every week before enzyme replacement. The

pa ent showed increasing concentra ons of a peak P-1.5/0.547 which is rela-

ted to acetone [67-64-1] over the me.

MotheMothMotheMotheMothtt rFatheFathethhhatheFatheatheerrrrrrrr

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aa yyeaar, aalllllllllyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyy,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

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