Occurrence, distribution and fate of pharmaceuticals and further polar

contaminants in the marine environment

DISSERTATION

zur Erlangung des Doktorgrades des Fachbereichs Chemie der Universitt Hamburg

vorgelegt von

Stefan Weigel

aus Hamburg

Hamburg 2003

The present thesis was carried out between August 1998 and October 2003 at the University of Hamburg, Institute of Organic Chemistry, in the research group of Prof. Dr. H. Hhnerfuss. University of Hamburg Institute of Organic Chemistry Martin-Luther-King-Platz 6 20146 Hamburg Germany http://www.chemie.uni-hamburg.de/oc/hfuss/

1. Reviewer: Prof. Dr. H. Hhnerfuss

2. Reviewer: Prof. Dr. Dr. h.c. W. Francke

Examen rigorosum: 12 December 2003

I

Table of contents

1 INTRODUCTION............................................................................................................ 1 1.1 Contamination of the marine environment.......................................................... 1 1.2 Pharmaceuticals and personal care products (PPCPs) in the environment ..... 4

1.2.1 Background...................................................................................................... 4 1.2.2 Relevance ........................................................................................................ 7 1.2.3 Metabolism....................................................................................................... 8 1.2.4 Caffeine............................................................................................................ 9

1.3 Objectives.............................................................................................................10 2 ANALYSIS OF POLAR ORGANIC COMPOUNDS FROM AQUEOUS MATRICES .....11

2.1 Extraction .............................................................................................................11 2.1.1 SPE for marine chemistry................................................................................12 2.1.2 SPE of pharmaceuticals ..................................................................................14 2.1.3 Comparison of different polymeric sorbents for the simultaneous extraction

of acidic, neutral and basic pharmaceuticals from water..................................16 2.2 Sequential elution ................................................................................................24 2.3 Clean-up, derivatisation.......................................................................................24 2.4 Instrumental analysis...........................................................................................25 2.5 Method validation.................................................................................................27

2.5.1 Quantification of pesticides, industrial chemicals and pharmaceuticals from marine large volume samples..................................................................28

2.5.2 Quantification of PPCPs from 1 L samples......................................................31 3 NON-TARGET SCREENING OF MARINE SAMPLES..................................................35

3.1 German Bight .......................................................................................................35 3.2 North Sea ..............................................................................................................47 3.3 Verification and relevance of identified compounds .........................................49

3.3.1 Pesticides........................................................................................................50 3.3.2 Industrial chemicals.........................................................................................53 3.3.3 Pharmaceuticals..............................................................................................63 3.3.4 Bromoorganic compounds...............................................................................66

3.4 Troms-Sound......................................................................................................70 3.5 Conclusions..........................................................................................................73

4 QUANTIFICATION OF SELECTED COMPOUNDS IN THE NORTH SEA ...................75 4.1 Pesticides .............................................................................................................76 4.2 Industrial chemicals.............................................................................................79 4.3 Pharmaceuticals and personal care products ...................................................81

4.3.1 Distribution in the North Sea............................................................................82 4.3.2 Transition river - sea........................................................................................85

4.4 Conclusions..........................................................................................................87 5 PHARMACEUTICALS IN THE ENVIRONMENT...........................................................88

5.1 Introduction ..........................................................................................................88 5.2 Determination of PPCPs in samples from Troms/Norway...............................89

5.2.1 Sampling campaign 2001: Seawater ...............................................................89 5.2.2 Sampling campaign 2002: Sewage .................................................................90 5.2.3 Sampling campaign 2002: Seawater ...............................................................93

5.3 Determination of PPCPs in samples from Hamburg/Germany .........................96 5.4 Concentration and metabolite patterns of ibuprofen.........................................99 5.5 Conclusions........................................................................................................101

6 SUMMARY..................................................................................................................102

II

7 ZUSAMMENFASSUNG ..............................................................................................105

8 EXPERIMENTAL ........................................................................................................108 8.1 Instruments.........................................................................................................108 8.2 Preparation of artificial seawater ......................................................................109 8.3 Chemicals ...........................................................................................................110

9 REFERENCES............................................................................................................112

ANNEX...........................................................................................................................127

III

List of figures Figure 1: General water circulation in the North Sea ............................................................. 2 Figure 2: Anticipated exposure routes of pharmaceuticals from use in human and

veterinary medicine ................................................................................................ 6 Figure 3: Metabolism of ibuprofen in humans, including renal excretion rates and

chiral aspects ......................................................................................................... 9 Figure 4: Method for the extraction of large volume North Sea water samples .....................13 Figure 5: Method for the extraction of 1 L water samples .....................................................14 Figure 6: Chemical structures of selected polymeric sorbents ..............................................17 Figure 7: Chemical structures of the compounds included in the sorbent comparison

study......................................................................................................................18 Figure 8: HPLC-chromatogram of a standard solution of the test compounds .....................19 Figure 9: Derivatisation of acidic and phenolic analytes with methyl chloromethanoate........25 Figure 10: Modified method for the quantitative determination of neutral and acidic

analytes from 20 L seawater samples..................................................................29 Figure 11: Chemical structures of the neutral, acidic and phenolic target analytes ...............31 Figure 12: Method for the determination of basic, neutral, and acidic compounds

from water samples .............................................................................................32 Figure 13: Position of the sampling location DB30 within the German Bight .........................36 Figure 14: Sampling positions within the North Sea..............................................................47 Figure 15: Chromatograms (GC-MS, full scan, TIC and extracted ion traces) of

pesticides identified in fraction 5 of sample DB30-3.............................................51 Figure 16: Mass spectra (EI, 70 eV) of pesticides identified in fraction 5 of sample

DB30-3 and from the respective standards..........................................................52 Figure 17: Chromatograms (GC-MS, full scan, extracted ion traces) and spectra

(EI, 70 eV) of desethylatrazine (left) and desethylterbuthylazine (right) in fraction 5 of sample DB30-3 and in a standard solution ..................................53

Figure 18: Chromatograms (GC-MS, TIC and extracted ion traces 146 and 148)