Analytical methods for the determination of pharmaceuticals in aqueous environmental samples

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Abstract

Recently several methods have been developed for the determination of drugs and their metabolites in the lower ng/l range using solid phase extraction (SPE), derivatization, detection and confirmation by gas chromatography/mass spectrometry (GC/MS) and GC/MS/MS or LC–electrospray tandem MS (LC–ES/MS/MS). A wide range of pharmaceuticals from different medicinal classes can be determined down to the lower ng/l range. Due to the basically elevated polarity of pharmaceuticals either analysis by LC–ES/MS/MS or an efficient derivatization prior to measurements by GC/MS are mostly essential. A direct comparison of GC/MS and LC–ES/MS/MS displayed that only the latter allows for the analysis of the extreme polar betablockers atenolol and sotalol due to an incomplete derivatization of the functional groups. Further, the relative standard deviation using LC–ES/MS/MS was lower. However, when analyzing highly contaminated samples such as sewage a suppression of the electrospray ionization is likely to occur. Thus, to guarantee accurate and reproducible data either an efficient clean-up step has to be included into the sample preparation or an appropriate surrogate standard has to be spiked prior to SPE enrichment.

Introduction

In human medicine annual drug prescriptions amounts to many tons per year, with some 100 tons in Germany alone [1]. This latter amount underestimates the total usage of drugs in the country – it does not include those which can be purchased without a pharmacy prescription and those procured illegally. About 3000 different compounds are used as constituents of medicinal products in human and veterinary medicine and comprise a wide range of different chemical structures. Because of the large number of compounds, to which should be added the huge number of excreted metabolites, it appears to be nearly impossible to develop analytical methods for all these substances in environmental samples. Therefore, a preselection is essential in developing methods for the potential environmentally relevant compounds. To preselect, the following criteria have been considered: (i) elevated annual prescription quantities, (ii) effect doses/concentrations, (iii) pharmacokinetic behavior (e.g. metabolism, urinary/fecal excretion rate).

Some endocrine active drugs possess an extremely high biological potency down to the μg/day doses, therefore it is very likely that they also cause effects at very low concentrations in the environment. For example, the contraceptive 17α-ethinylestradiol adversely effects the reproduction of zebrafish (Danio rerio) at concentrations as low as 1 ng/l [2]. The pharmacokinetic behavior directly influences the potential environmental contamination. A drug which is only excreted as metabolites should in general not be found in sewage and the environment. Thus, for those compounds it makes more sense to monitor the stable excreted principal metabolites. Pharmacokinetical data show that human excretion rates of unchanged drugs sometimes even exceed 50%. Additionally, excreted metabolites formed by conjugation with glucuronic acid or other polar compounds are likely to be cleaved by microorganisms into the unchanged pharmaceuticals 3, 4, and hence the relevant environmental concentration will increase.

Due to such high usage levels and excretion rates, detectable concentrations of drugs and their metabolites should not be unexpected in sewage.

This review summarizes those analytical methods which allow for the determination of drugs in different aqueous matrices down to the ng/l range.

Section snippets

Analytical methods

Several analytical methods have been published concerning the determination of pharmaceuticals in biological samples such as serum, blood or urine within the μg/l range 5, 6, 7, 8, 9, 10, 11, 12, 13. The detection was mainly performed by high performance liquid chromatography (HPLC), gas chromatography/mass spectrometry (GC/MS) or GC/FID, and de Jong et al. [8]have applied GC/MS/MS. Antiepileptic drugs such as carbamazepine have been detected in human serum after a solid phase extraction (SPE)

Exposure of the environment to pharmaceuticals

Using the methods discussed above, 36 of 55 pharmaceuticals and five of nine metabolites were quantified in at least one German STP effluent. In general, the removal in the municipal STP exceeded 60% [51]. The highest concentrations of drug residues were measured for the antiepileptic carbamazepine with a maximum of 6.3 μg/l (Table 11). However, X-ray contrast media were found in concentrations as high as 15 μg/l for iopamidol and 11 μg/l for iopromide [52]. In 40 German rivers and streams 31

Conclusion

The analytical methods discussed above were used for the determination of pharmaceuticals in different aqueous matrices. Highly polluted sewage was investigated as well as river and drinking waters. Many of the investigated drugs could be detected in influents and effluents of German municipal STPs as well as in rivers and streams. Hence, the applied methods which include GC/MS, GC/MS/MS, and mainly LC–ES/MS/MS are appropriate for the determination of pharmaceuticals and phenolic antiseptics in

Acknowledgements

This study was financially supported by grants of the Ministry of Education and Research (BMBF)/Germany and the Hessian Ministry for Environment, Energy, Youth, Family and Health.

Thomas Ternes graduated with a diploma in Chemistry 1989 and received his PhD on the analysis of organic contaminants in water and fish by GC/MS at the University of Mainz in 1993. Since 1994 he is coordinating and managing research projects at the ESWE-Institute for Water Research and Water Technology. He is a lecturer at the University of Mainz for the analysis of organic contaminants in the environment. Since 1994 he is dealing with the analysis of organic compounds especially

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    Thomas Ternes graduated with a diploma in Chemistry 1989 and received his PhD on the analysis of organic contaminants in water and fish by GC/MS at the University of Mainz in 1993. Since 1994 he is coordinating and managing research projects at the ESWE-Institute for Water Research and Water Technology. He is a lecturer at the University of Mainz for the analysis of organic contaminants in the environment. Since 1994 he is dealing with the analysis of organic compounds especially pharmaceuticals and personal care products in wastewater, river and drinking water.

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