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I


Extractability of drug traces and metabolites from water media by
polyurethane foam and block copolymer membranes



Der Fakultät für Naturwissenschaften
Department Chemie
der Universität Paderborn

Zur Erlangung des Grades eines
Doktors der Naturwissenschaften


Dr. rer. nat.
Vorgelegte Dissertation
Von
Intisar A. F. EL- Sharaa, M.Sc. in Chemistry
aus Benghazi/Libyen
Paderborn 2010 II
The present work has been carried out from May 2005 until December 2009 at the
University of Paderborn, Faculty of Science, Department of Chemistry under
supervision of Prof. Dr. M. Grote.























Referent Prof. Dr. Manfred Grote
Koreferent Prof. Dr. Wolfgang Bremser
Eingereicht am 04.05.2010
Tag der mündlichen Prüfung: 26.05.2010



III
Aknowledgements

First of all, I would like to express my deepest sense of gratitude to my supervisor,
Prof. Dr. Manfred Grote, for his patient guidance, encouragement and advice
throughout this study.
I would also like to thank Prof. Dr. Wolfgang Bremser for scientific support, and his
coworker Dr. Björn Weber for synthesizing polymer membranes which were used in
this study.
I am thankful to my laboratory members, Dr. Nabil Al. Hadithi, Dipl. Chem- Ing.
Didem Hanim Meric, Dipl. Chem- Ing. Reinhard Michel, Dipl- Chem. Manuel Ewe,
Dipl- Chem. Mareike Busse, Staatl. Gepr. LM Chem. Farzana Chowdhury and Mrs.
R. Knaup for creating an environment comfortable working and welcoming me at the
university making me feel at home, and teaching me some German culture. It is truly
an honor for me to know each and everyone.
Special thanks to Reinhard and Manuel for sharing with me a lot invaluable
knowledge regarding instrument operation methods and, which will be very helpful
and useful for my future scientific live.
I would also like to thank Dr. Ishtiaq Ahmed, and Dr. Nabil Bader for proof-reading my
thesis and providing valuable feedback.
I deeply thank my true and faithful friends Khawla Franka, Fhatiha Ouazir, Ainas
ELshara, Aziza Ahmida, Sheelan Khasro and encouragement from all of my friends.
My sincere thanks go to the Yesilyurt and Gürbüz families for helping me and they
are really a family to me in this country.
I thank the Secretariat of higher education of Libya for giving me Ph.D. scholarship.
Finally, I extend my warmest thanks to my wonderful big family for being a source of
inspiration and continuously encouragement in all my life directions.
First and foremost, I would like to thank God for giving me this chance, and this
paves the way for a prolific scientific career.

Intisar EL-Sharaa
01.05.2010 IV







Dad’s spirit and Mum,
My Family,
My relatives and friends.


















V
Table of Contents

1 Pharmaceuticals in the aquatic environment 4
1.1 Sources and origins 8
1.2 Fate of drugs after medical application 9
1.3 How do the drugs get into the water? 10
1.4 Possible effects on the environment 12
2 Aim of the study 14
3 Pharmaceuticals used in this study: basic properties 17
3.1 Antibiotics 17
3.2 Use of antibiotics 17
3.3 Antibacterial resistance and the environment 18
3.4 Tetracyclines 20
3.4.1 Tetracycline (TC) 20
3.4.1.1 Characterization 20
3.4.1.2 Environmental behaviour 21
3.4.2 Chlortetracycline (CTC) 22
3.4.2.1 Environmental behaviour 22
3.5 Sulfonamides 23
3.5.1 Sulfamethoxazole (SFM) 23
3.5.1.1 Metabolism 24
3.5.1.2 Environmental effects 25
3.6 Neuroactive compounds ( antiepileptic, antidepressants )-
Carbamazepine (CBZ) 27
3.6.1 Metabolism 28
3.6.2 Environmental behaviour 28
3.6.3 Environment effects 29
3.7 Analgesics and ant-inflammatory drugs 30
3.7.1 Diclofenac (DCF) 30
3.7.1.1 Metabolism 30
3.7.1.2 Environmental behaviour 31
3.7.1.3 Environmental effects 32
3.7.2 Ibuprofen (IBU) 32
3.7.2.1 Metabolism 32 VI
3.7.2.2 Environmental behaviour 33
3.7.2.3 Environmental effects 33
4 Analytical extraction techniques 34
4.1 Principle of polymeric membrane 36
4.1.1 Polymeric membrane extraction (PME) 36
4.1.2 Diffusion in polymers 37
Polyurethane Foam (PUF) as a sorbent in analytical chemistry 5
38
5.1 Fundamental chemistry of polyurethane foam 38
5.2 Polyurethane foam: The sorbent material 39
5.3 Polyurethane foam preparation 40
5.3.1 Physical and chemical properties of polyurethane foam 41
5.3.2 Option for separations using polyurethane foam membranes 43
5.4 Mechanistic approaches to the sorption processes on PUF 44
5.5 PUF as sorption Techniques from aqueous media 44
5.6 Using polyurethane foam for removal of organic contaminants 45
6 Novel blockcopolymers 50
6.1 Synthesis and structure of membranes 50
6.1 Novel polymeric membrane based on diphenylen 50
6.1.2 Composition of polymer membrane foam 52
7 Results and discussion – polyurethane foam 53
7.1 Methodical approach 53
7.1.1 Chromatographic methods 53
7.2 Extraction of the drugs and metabolites by PUF 54
7.2.1 Materials and methods 54
7.2.2 Polyurethane types used 54
7.3 Extractability of N-4-acetylsulfamethoxazole (ASFM), SFM and 56
CBZ by PUF
7.3.1 Sorption of ASFM- Effect of shaking time and PUF- type 57
7.3.2 Effect of pH on the sorption 59
7.3.3 Effect of salts on the sorption 64
7.3.4 Recovery process of drugs from loaded PUF 65
7.4 Sorption of Tetracyclines (TCs) by PUF 70
7.4.1 Influence of pH media on the sorption of TCs by PUF 70 VII
8 Sorption of drugs by novel polymeric membranes (BM) 74
8.1 Extractability of polymer membranes for SFM, CBZ, DCF and
IBU 74
8.2 Extraction of tetracyclines drugs by novel polymer membranes 78
8.3 Effect of pH on the sorption by polymeric membrane 81
8.3.1 Active drugs SFM, CBZ, DCF and IBU 81
8.3.2 Influence of pH on the sorption of TCs 82
8.4 Recovery of TCs drugs from loaded BM34 and BM43 polymers 85
8.4.1 Extraction from acidic media 85
8.4.2 Recovery of the drugs loaded on BM34 and BM43 polymers 87
9 Results and Discussion – Comparative discussion 92
9.1 Comparative study between the extraction and elution behaviour
of PUF and BM 92
9.2 Comparative study of extraction by polymer membranes and
other extraction techniques 94
10 Summary 96
11 Experimental 99
12 References 114



I
List of Figures

Fig. 1.1 EU-wide veterinary medicine in the drug groups established in
2006 5
Fig. 1.2 Sources and distribution of pharmaceuticals in the environment 11
Fig. 3.1 Major pathways of the oxidative metabolism of SFM in human 24
Fig. 3.2 Major pathways of the oxidative metabolism of CBZ in human 28
Fig. 3.3 Major oxidative metabolism products of DCF in urine 31
Fig. 3.4 Major pathways of the oxidative metabolism of IBU in human 33
Fig. 5.1 Scanning electron micrograph of typical polyurethane foam
structure 39
Fig. 6.1 Scanning electron-micrographs of a typical BM structure and
layer structure of polymer membrane 52
Fig. 6.2 Monomers of polymer membrane compounds investigated 52
Fig. 7.1 Calibration curve of target drugs (CBZ, SFM and metabolite
ASFM) 56
Fig. 7.2 Effect of PUF types on sorption of ASFM 58
Fig. 7.3 Influence of pH on the extraction of target compounds by PUF
(CBZ, SFM and ASFM) 61
Fig. 7.4 Effect of pH on the sorption of drugs by PUF
61
Fig. 7.5 Influence of salts on target drug extraction at pH 3 64
Fig. 7.6 Size effect of ionic radii of various metal cations on the sorption
of ASFM 65
Fig. 7.7 Extraction and recovery procedures by meansPUF 66

Fig. 7.8 Influence of shaking time on the recovery of target drugs from
PUF loaded with various eluting agents 67
Fig. 7.9 Extraction and recovery of drugs with different solvent from PUF 67 II
Fig. 7.10 Effect of pH and time on extraction of TCs drugs by PUF 72
Fig. 7.11 Effect of pH on extraction of tetracycline’s 72
Fig. 8.1 Monomers used for the synthesis of novel block copolymer
membrane compounds 75
Fig. 8.2 Extraction of drugs by polymer membranes as a function of
time 77
Fig. 8.3 Comparison of the extractability of active drugs by BM42 and
BM43 78
Fig. 8.4 Extractability of TCs polymer membranes as a function of time 80
Fig. 8.5 Extraction of active drugs at pH 3 and by polymers BM42 and
BM43 as function of time 81
Fig. 8.6 Influence of pH on the extraction of drugs by polymer
membranes 82
Fig. 8.7 Extraction of TCs drugs at pH 3 by polymer membranes BM42,
BM 43 and 34 84
Fig. 8.8 Influence of pH on extraction of TCs drugs by BM43 85
Fig. 8.9 Extraction of target active drugs at pH 3 by selected polymer
membranes (BM43 and BM34) 87
Fig. 8.10 Recovery of drugs from loaded BM34 with acetone and
acetonitrile as function of time 89
Fig. 8.11 Recovery of drugs from loaded BM43 with acetone and
acetonitrile as function of time 89
Fig. 8.12 Comparison of recovery processes for both MB34 and BM43
Polymeric membrane with different eluting agents 90
Fig. 9.1 Comparison of extractability of selected drugs by PUF and BM
93 membranes
Fig. 9.2 Comparison between BM34 and BM43 polymer membranes
94
Fig. 11.1 Purification of PUF foam, a) acetone after foams treatment, b)
pure acetone 101
Fig. 11.2 HPLC-UV chromatogram:blank sample of BM34 102 III
Fig. 11.3 HPLC-UV chromatogram for the selected drug metabolite and
active drugs by using different methods 111































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