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Drug delivery related to metabolites in human breath – first results of long term clinical studies using MCC/IMS * Korea InsƟtute of Science and Technology Europe ForschungsgesellschaŌ mbH (KIST Europe) Campus E 7 1 - 66123 Saarbrücken - Germany phone + 49 (0) 681 9382 229 - fax + 49 (0) 681 9382 240 hƩp://www.kist-europe/r_cd_jibb.html hƩp://www.kist-europe.com hƩp://www.kist-europe.de Contact: PD Dr. Jörg Ingo Baumbach Head of Department Microfluidics and Clinical DiagnosƟcs [email protected] Part of a IMS-Chromatogram of human breath * Kor * Kor * Kor * Kor * Kor * Kor * Kor * Kor * Kor * Kor * Kor *K * Kor Korea In ea In ea In ea In ea In ea In ea In ea In a In ea In ea In ea ea In a sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu Ɵtu sƟtu sƟtu Ɵt te of te of te of te of te o te of e of te of te of te of te of e o e of eo te of Scie Scie Scie Scie Scie Scie Scie Scie Scie c Scie cience a nce a nce a nce a nce a nce a nce a nce a nce a ce nce a e ea e and Te nd Te nd Te nd Te d Te nd Te nd Te nd Te d Te nd Te nd T nd Te nd Te nd chnol chnol c chnol chnol chnol chnol chnol chnol chnol o ol o chnol ol ol chnol o ol c l hno ogy E ogy E ogy E ogy E ogy E ogy ogy E ogy E ogy E ogy E ogy E ogy E ogy E ogy E o ogy Europe urope uro urop urope urop urop urope r urope urope pe pe pe urope urope pe pe e rope rope e e e Fors Fors Fors Fors Fors Fors Fors Fors Fors Fors ors Fors ors Fors or F F F F F chung chung chung chung chung chung chung chung chung chung chung chung chung chung g chungsges sges sge sgese sg g sgese sges sgese sgese sgese sgese sgese sgese sgese es se se s se g se e llsch llsch llsch llsch llsch lsch llsc llsc llsc llsch lsch llsch h llsch h h h h lsch haŌ m aŌ m aŌ m aŌ m aŌ m aŌ m aŌ m aŌ m aŌ m m Ō m m Ō m m m m Ō bH (K bH ( bH (K bH (K H (K H (K H H bH (K H H H (K K H H ( H (K H bH (K H H H (K ( IST E IST E IST E IST E IST E ST E IST E ST E ST ST IST E ST E ST E ST E E ST E ST E T ST IST E urope urope urope urope urope rope urope urope ope pe pe e rope ope pe e rop urope p ) ) ) ) ) ) ) ) ) ) ) ) b b b b b b b k k k k b b k hƩp: hƩp: hƩp: hƩp: hƩp: hƩp h hƩp: hƩp: hƩp: Ʃp: hƩp: hƩp: p: Ʃp hƩp: p: hƩp: hƩp: hƩp: hƩp Ʃp h //www //ww //www //www //www /www //www //www www www //www //www //www //www //www //www /www w //www // //www //www //www / w ww w .kist .kist .kis .kis .kist .kist .kist .kist .kis .kis .kist .kis .kis is .kist .kis i .ki .kis .kis s s .kis kis .kis i -euro -e -euro -euro -euro euro euro euro euro euro euro euro euro euro euro uro eur euro - -euro e pe/r_ pe/r pe/r_ pe/r_ pe/r_ pe/r_ pe/r pe/r_ e/r e/r_ pe/r_ e/r e/r e pe/r_ pe/r_ pe/r_ / pe/r pe/r pe/r_ pe/r_ pe/ p r p r pe/ cd_ji cd_ji cd_ji cd_ji cd_ji d cd_ji cd_ji cd_ji cd_ji c cd ji cd_ cd_ji cd_ji d_ji cd_ i d_ji ji ji c _ji i i jibb.ht bb.ht bb.ht bb.ht bb.ht bb.ht bb. bb bb. bb.h bb.h bb. bb. bb.ht .ht ht bb.ht bb. bb b . .h h b h m m m ml ml ml ml ml ml ml ml ml ml m ml m ml m m h h h h h h h h // // // // / / / / / / / / / / / / / k k k k k k k Conta Conta Conta Conta Conta on onta Conta ont ont ont Conta ont Conta on Conta Conta Conta Conta o ont t n o o ct: ct: ct: ct: ct c ct ct: ct: ct: t ct PD PD PD PD PD PD PD D PD D PD D PD PD PD P PD P PD D D Dr J Dr. J Dr. J Dr Dr. Dr r. 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J Dr. J J r D J örg I örg I örg I örg I örg örg örg I örg örg I örg I örg I örg I örg I örg I örg örg örg I rg I rg g örg I örg I ör ngo B ngo B ngo B go B go g go B go B go B ngo B ngo B go B go B go B go B go B o oB go B go B go B ngo go go B ngo B go ngo o aum aumba aumba aumba aumba aumba aumba aumba umba u aumba umba aumba aumba umba um aumba mba umba aumba aumb b au aumb mb aumb mba a a b u a m ch ch ch ch c ch ch ch ch ch c ch c c ch ch ch h d d d d d f f fl fl fl fl d d d d d d d d d d d d d l l l l l * Kor * Kor * Kor * Ko * Kor * Kor * Kor * Kor * Kor * Kor * Kor * Kor * Kor * * Kor ea ea In ea In ea In ea In ea In ea In ea In ea In ea In ea In ea In a In a In sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu sƟtu Ɵt te of te of te of te of te of e of te of te of te of e of te of e of e of te o e of Scie Scie Scie Scie Si Si Scie Scie Scie Scie Scie Si Scie Scie nce a nce nce a nc nce a nce a nce a nce a nce a nce a nce a nce c nd Te nd Te nd Te nd Te nd Te nd Te nd Te dT Te nd Te nd Te nd Te nd Te chnol chnol chno chnol chnol chno hno chnol no hn chnol no chnol chn chn no chnol hno no no ogy E ogy E ogy E ogy E ogy E ogy E ogy E ogy E gy E ogy E gy E ogy E E urope uro urope urope urope urope uro urope uro uro uro uro ope pe pe pe uro e p r Fors Fors Fors Fors Fors Fors For or Fors Fors ors Fors Fors ors ors chung chun chung chung chung chung chun chung hung chung chun chung g g chung hung sges sges sges sgese sgese sgese gese gese gese gese gese ges g ges ges se sg se s se e e es llsch llsc llsc lsch llsch llsch llsc llsc lsch llsch ch ch ch lls llsch llsch llsch ch ch c aŌ m aŌ m aŌ m aŌ m aŌ m aŌ aŌ m Ō Ō Ō m aŌ m aŌ m Ō m Ō m aŌ m aŌ m Ō Ō aŌ Ō m m Ō m m bH (K bH (K bH (K bH (K bH (K H H( H (K H( H (K bH (K bH (K H H( H (K K H( bH (K bH (K H( H( bH (K H H ( ( IST E IST E IST E ST E ST E TE TE TE TE E TE E TE TE TE T TE IST E T E E urope urope urope urope urope urope rope urope urope e pe pe pe rope e e ) ) ) ) ) ) ) ) ) ) ) ) hƩp: hƩp: hƩp: hƩp hƩp: hƩp hƩp: hƩp: hƩ hƩp: hƩp: hƩp: Ʃp: hƩp: hƩ hƩp Ʃ hƩp hƩ Ʃ h h //www //www //ww //www //www //www //www //www www /www //www //www //www //www //www //ww //www //www //www ww // kist kist kis kist kist kist kist kist kis kis kis ki is kis kist kis kis kis i kis kis ki ki k e euro euro euro euro euro euro euro euro euro u euro euro euro uro euro pe/r pe/r pe/r pe/r pe/r pe/r pe/r pe/r pe/r e/r e/r e/ pe/r /r pe/r pe/r pe/r pe/r e/r / /r e/r e e e e/r e cd cd cd d d cd dj cd ji dj d ji d ji cd ji cd ji cd ji cd ji cd d dj d cd cd d d bb ht bb ht bb ht bb ht bb ht bb ht bb ht b bb ht bb ht bb ht b ht bb ht b b bb ht bb ht bb ht bb ht bh bb ht b ht b bb ht b ht m m m m m m m m ml ml ml ml ml ml ml m m m m ml m Conta Conta Conta Conta Cont Conta Conta Conta Conta Conta ont onta onta ta nta Conta a ta Conta onta onta Conta o on o t c ct: ct: ct: ct: ct: ct: ct: ct c ct: : PD PD PD PD D D D D D PD P PD D D PD PD D Dr J Dr J Dr J Dr J Dr J Dr J r Dr Dr J Dr J Dr J r Dr D J r J Dr J rJ r örg I örg I örg I ö örg I örg I örg I örg I örg I örg örg örg örg I örg I örg örg I örg I örg I örg örg I örg I örg ö ngo B ngo B ngo B ngo B go B go B go B ngo B go go B oB ngo B go B go B B go B go B go B go B B o B aumba aumba aumba aumba umba aumba aumba aumba aumba umba aumba umba umba aumba aumba umba b aumba a aumba aumba aumba aumba aum a a au a h h h ch ch c ch ch ch ch ch ch ch ch h h ch ch h ch c c M. Westhoff 1 , P. LiƩerst 1 , S. Maddula 2 , J.I. Baumbach 2,3 1 Lung Clinic Hemer, Theo-Funccius-Str. 1, 58675 Hemer, Germany 2 KIST Europe, Department Microfluidics and Clinical DiagnosƟcs, Campus E 71, 66123 Saarbrücken, Germany 3 B&S AnalyƟk, BioMedicalCenter Dortmund, OƩo-Hahn-Str. 15, 44227 Dortmund, Germany Acknowledgements The financial support of the Ministry of EducaƟon, Science and Technology (MEST) of the Republic Korea is acknowledged thankfully. Part of the work on this paper has been supported by Deutsche For- schungsgemeinschaŌ (DFG) within the CollaboraƟ- ve Research Center (Sonderforschungsbereich) SFB 876 „Providing InformaƟon by Resource-Constrai- ned Analysis“, project TB1 “Resource-Constrained Analysis of Spectrometry Data“. In addiƟon, 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. 0 62 124 186 248 40 60 80 100 120 140 160 0 62 124 186 248 0,002 0,004 0,006 0,008 0,010 0,012 0,014 0,016 GAG GAG / a.u. IMS - Peak height Signal height / a.u. 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The e The e The e The e The e The e The e The e The e The e The e The e The e The e he e he The e xperi xperi xper xperi xperi xperi xperi xperi xperi xperi xpe xperi xperi xperi xperi e menta menta menta menta menta menta menta menta menta menta menta menta menta menta n a t l wor l wor l wor l wor l wor l wor l wor l wor l wor l wor l wor l wor l wor wor o l wor o k des k des k des k des k des k de k des k des k des k des k des k des k des k des d k cribe cribe cribe cribe cribe cribe cribe cribe cribe cribe cribe ribe cribe cribe cribed was d was d was d was d was d was d was d was d was d was d was d was d was d d was d was d d was carr carr carr carr carr carr carr carr carr carr carr carr carr carr arr c ied o ied o ied o ied o ied o ied o ied o ied o ed o ied o ed o ied o ied o ied out ut ut ut ut ut ut ut ut ut ut ut ut ut partl partl partl partl partl partl partl partl partl partl partl partl partl partl partl rtl t y at y at y at y at y at y at y at y at y at y at y at y at t y at y at y at ISAS ISAS ISAS ISAS SAS ISAS ISAS ISAS ISAS ISAS ISAS ISAS ISAS ISAS SAS ISAS S ISAS Dortm Dortm Dortm Dortm Dortm Dortm Dortm Dortm Dortm Dortm Dortm Dortm Dortm Dortm ortm Do D und, und, und, und, und, und, und, und, und, und, und, und und, und, und, n nd d Germa Germa Germa Germa Germa Germa Germa Germa Germa Germa Germa Germa Germa Germa Germany. ny. ny. ny. ny. ny. ny. ny. ny. ny. ny. n ny ny. 40 60 80 100 186 248 186 248 GAG / a.u d The concentraƟons were higher than the concentraƟons of all paƟents ever tested with MCC/IMS. Furthermore, a peak P-77.2/0.601 was found, which decreased aŌer few weeks of therapy and needs further biochemical characterisaƟon. Parallel GC/MSD invesƟgaƟons 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 paƟents with metabolic disorders might give further informaƟon about metabolism, especially under enzyme replace- ment therapy. PaƟent Father Mother GAG Part Part Part Part Part art r P PaƟe PaƟe PaƟe PaƟe PaƟe e e ent nt nt nt n n n Hunter disease is a mucopolysaccharidosis for which enzyme replacement therapy with idursulfase has been offered for 3 ye- ars. Therapy can be monitored by the urinary concentraƟon of dermatan sulfate and heparin sul- fate. A 38-year-old male person suffering from Hun- ter disease has been treated with idursulfase for a year, showing dramaƟc clinical improvement. AddiƟonally, the paƟent had breath analysis using MCC/IMS every week before enzyme replacement. The paƟent showed increasing concentraƟons of a peak P-1.5/0.547 which is rela- ted to acetone [67-64-1] over the Ɵme. Mothe Moth Mothe Mothe Moth t r Fathe Fathe th h athe Fathe athe er r r r r r r r - - - - - - - - n n n n- - a a y yea ar, a al l l l l ly y y y y y ,

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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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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

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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.

0 62 124 186 24840

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0 62 124 186 248

0,002

0,004

0,006

0,008

0,010

0,012

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 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

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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.

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Production of Secondary Metabolites

Food Biotechnology- Metabolites

Primary metabolites

Secondary metabolites - Napa Valley College · Metabolites Metabolites are all the products of metabolism A primary metabolite is directly involved in normal growth, development,

Secondary metabolites

Endogenous Bile Acid Metabolites as Biomarkers for … · Endogenous Bile Acid Metabolites as Biomarkers ... Endogenous Bile Acid Metabolites as Biomarkers for CYP3A Tommy B. Andersson

Seconadary Metabolites and Pathways

Plant Secondary Metabolites as Defenses, Regulators, and Primary … · Topical Review Plant Secondary Metabolites as Defenses, Regulators, and Primary Metabolites: The Blurred Functional

OPEN ACCESS metabolites - MDPI

Integration of Metabolism. FUELS, METABOLITES AND DISORDERS FUELS URINE BILE/FECES METABOLITES METABOLITES Starch, Glucose NH 4, + SO 4 2-, HPO 4 2- Cholesterol,

Non-invasive monitoring of cortisol metabolites level in ... · Non-invasive monitoring of cortisol metabolites level in ... Non-invasive monitoring of cortisol metabolites level

PRIMARY AND SECONDARY METABOLITES

Metabolites 02 00303

Industrial Microbiology Cells Bioconversion Cells products Fungi (Yeasts) Streptomyces Primary Metabolites Secondary Metabolites

Predicting Metabolites - Lhasa Limited

Secondary Metabolites from Plants

Breath of Life - Avani Yoga Academy€¦ · The Breath of Vitality Vyana Vayu: The Breath of Integration Udana Vayu: The Breath of Ascent Samana Vayu: The Breath of Balance Apana

Metabolites Primary & Secondary

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List of metabolites

Petroleum Metabolites

Plant secondary metabolites

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Secondary metabolites (1)

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Reactive Metabolites PButler

Plant Metabolites

Seconadry metabolites

Anti metabolites

Secondary Metabolites from Plants Plant Secondary Metabolites

Breath gas metabolites and bacterial metagenomes from cystic … · spp. and Rothia mucilaginosa, and revealed the potential for 2,3- butanedione biosynthesis. Genes encoding 2,3-butanedione

Testing Urine Hormone Metabolites

Sec. Metabolites [Compatibility Mode]

Secondary Metabolites Pankaj Presentation