Quantitative on-line preconcentration-liquid chromatography coupled with tandem mass spectrometry method for the determination of pharmaceutical compounds in water
Graphical abstract
Introduction
Because of a continuous increasing consumption of pharmaceuticals, the problem of their presence in the environment and more particularly in water bodies is a serious environmental issue in France, and on wider scale, in industrialized countries. Most of pharmaceuticals are used for several decades but scientific studies dealing with this problem have been published in the last 15 years mainly related to the increase of analytical methodology performance [1], [2], [3]. The toxicity of these molecules, initially designed with biological effects for people or animals, may have a chronic impact on aquatic living organisms. Actually, the continuous presence of pharmaceuticals in water bodies even at very low concentration, can lead to unwanted biological effects on aquatic species. Pharmaceuticals are continuously released in natural waters via wastewater treatment plants but also hospitals, industrials, households and farming [4]. It is therefore of great concern to try to broaden the current knowledge and to determine the impact of pharmaceutical pollution on the environment.
Several surveys highlight the occurrence of pharmaceutical residues in the aquatic and terrestrial compartments [[5], [6] for example]. The low concentrations usually determined in natural waters require the development of sensitive analytical methodologies, adapted to environmental matrices able to quantify pharmaceuticals at ng L−1 level or less. Analytical methods mainly consist in multi-residue methods, with mass spectrometry coupled to chromatographic techniques (gas [7], [8], [9], [10] or liquid [11], [12], [13], [14], [15]). An extraction-concentration step is necessary prior to chromatographic analysis. Nowadays, the extraction step is commonly performed with an off-line solid phase extraction procedure to be specific and sensitive enough. However, more recently, the development of on-line solid phase extraction with new commercially available apparatus has been proposed [16], [17], [18].
Two different approaches of on-line extraction have been described in the literature. The first set consists in small columns that can be used several times and the second one is similar to off-line usual solid phase extraction with single use cartridges [19]. This technique was firstly applied for pesticides in waters [20], [21] and recently extended for pharmaceuticals. On-line methods have initially been developed for the quantification of few compounds (<10) [16], [22], [23]. With further development, methods have been proposed for multi-class analyses [24], [25], [26]. By comparison with off-line solid phase extraction, these methods are less time consuming and require a lower volume of sample. On-line methods are therefore financially more attractive than off-line methods as demonstrated by Trenhold et al. [18].
The aim of this work is to develop and to validate a sensitive and specific multi-residue method using on-line preconcentration-liquid chromatography–tandem mass spectrometry. The interest is to analyze a wide number of compounds with various physicochemical properties in very short time compared to the laborious off-line SPE. On-line analytical methods combining SPE and LC–MS/MS have already been reported for the determination of a broad range of pharmaceuticals (e.g. Ref. [26] for more than 40 compounds). However, these methods used an automated SPE system similar to the classical off-line usual solid phase extraction with single use cartridges. EQuan™ system uses a multiple used column for preconcentration step which can be used up to 400 times and is completely automatized. EQuan™ system works with a low sample volume (<5 mL) and the automation make it an ideal method for the analysis of a large number of samples with a reduction of interferences during sample handling and concentration. Moreover, on-line system can provide a significant advantage when crisis management following pollution is concerned. Actually, the possibility of directly injecting samples will give a rapid qualitative result.
Our method has been validated for 40 pharmaceuticals from different therapeutic groups in tap and surface waters. Its performances have been evaluated under the most rigorous conditions to ensure higher reliability. The on-line method uncertainty for each compound has been determined using two different approaches. The method will therefore be applied to large-scale surveys.
Section snippets
Materials and reagents
Pharmaceutical standards (purity >97%) were purchased from Sigma-Aldrich (St Louis, MO, USA) except for monensin provided by Fischer Scientific France (Waltham, MA, USA). Quality control (QC) solution was supplied by Cluzeau Info Labo (Sainte-Foy-La-Grande, France). Isotopically labelled compounds were purchased from C/D/N Isotopes (Quebec, Canada) except for chloramphenicol d5 and sulfamethoxazole d4 which were from Dr Ehrenstorfer (Augsburg, Germany) and acetaminophen d4 from LGC Promochem
Loading time and flow rate of the preconcentration step
The optimal loading conditions of the sample have to be determined in a first step. Indeed, the nature of the solvent, the loading time and flow rate influence the retention of analytes onto the preconcentration column. The highest retention of compounds has to be reached and early desorption of analytes has to be avoided. Purified water, without any organic solvent, has been used as carrier solvent to insure a better retention of more polar compounds.
Flow rate and loading time optimization has
Conclusion
Through this study, a multi-residue method by on-line preconcentration has been developed and validated for 40 pharmaceutical residues in drinking and surface waters with a wide variety of physicochemical properties. The low sampling volume (<5 mL) as well as a relatively short time of preparation and of analysis (20 min for negative mode and 28 min for positive mode) including preconcentration step, elution and detection are among the most significant advantages of this system by comparison with
Acknowledgements
The authors thank the reviewers of the paper for their very helpful comments. The authors acknowledge financial support from FEDER (no. présage: 33086), Conseil Général de la Dordogne and Thermo Fisher Scientific. LPTC thanks Anses for financial support (Toxstep project EST-09-57). The authors would also like to thank Agence de l’Eau Adour Garonne and Lyonnaise des Eaux Périgueux for their different contributions. SI gratefully acknowledges ANRT (Agence Nationale pour la Recherche et la
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