The aim of this study was to develop and optimise an analytical method for the quantification of a bactericide and 13 pharmaceutical products, including 8 antibiotics (fluoroquinolones, tetracyclines, sulfonamides, macrolide), in various aqueous environmental samples: soil water and aqueous fractions of pig slurry, digested pig slurry and sewage sludge. The analysis was performed by online solid-phase extraction coupled to ultra-high performance liquid chromatography with tandem mass spectrometry (online SPE-UHPLC-MS-MS). The main challenge was to minimize the matrix effects observed in mass spectrometry, mostly due to ion suppression. They depended on the dissolved organic carbon (DOC) content and its origin, and ranged between -22% and +20% and between -38% and -93% of the signal obtained without matrix, in soil water and slurry supernatant, respectively. The very variable levels of these matrix effects suggested DOC content cut-offs above which sample purification was required. These cut-offs depended on compounds, with concentrations ranging from 30 to 290 mgC/L for antibiotics (except tylosine) up to 600-6400 mgC/L for the most apolar compounds. A modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) extraction procedure was therefore optimised using an experimental design methodology, in order to purify samples with high DOC contents. Its performance led to a compromise, allowing fluoroquinolone and tetracycline analysis. The QuEChERS extraction salts consisted therefore of sodium acetate, sodium sulfate instead of magnesium sulfate, and sodium ethylenediaminetetraacetate (EDTA) as a ligand of divalent cations. The modified QuEChERS procedure employed for the extraction of pharmaceuticals in slurry and digested slurry liquid phases reduced the matrix effects for almost all the compounds, with extraction recoveries generally above 75%. The performance characteristics of the method were evaluated in terms of linearity, intra-day and inter-day precision, accuracy and limits of quantification, which reached concentration ranges of 5-270 ng/L in soil water and sludge supernatant, and 31-2400 ng/L in slurry and digested slurry supernatants, depending on the compounds. The new method was then successfully applied for the determination of the target compounds in environmental samples. (C) 2014 Elsevier B.V. All rights reserved.

Pharmaceutical products excreted by treated animals or humans are transferred to manure or wastewater, respectively. In wastewater treatment plants, they can be degraded and/or adsorbed into sludge. Therefore pharmaceuticals may be indirectly disseminated into the environment from the recycling of organic residues in agriculture, which is largely encouraged nowadays. Even though the European regulations on this usage do not include pharmaceuticals, they are considered as emerging pollutants due to their potential activity against non-target organisms and their potential risk of transfer towards aquatic ecosystems. It is thus necessary to estimate their available concentration, mostly present in soil water or in the aqueous phase of organic residues. These analyses represent a challenge, because of the trace-level concentration of pharmaceuticals in complex matrices. We developed an analytical method for the quantification of 14 pharmaceuticals (including 8 antibiotics) in various aqueous environmental samples: soil water and aqueous fractions of pig slurry, digested pig slurry and sewage sludge, which present a wide range of dissolved organic carbon (DOC) content [1]. The analysis was performed by online solid-phase extraction coupled to ultra-high performance liquid chromatography with tandem mass spectrometry (on-line SPE-UHPLC-MS/MS). During this development, we have been particularly confronted to the importance of matrix effects in mass spectrometry analysis. Indeed, undesirable molecules present in the samples can strongly modify the MS signal of the analytes, leading to a wrong quantification and an increase of quantitation limits. We thus proposed a criterion and methods to deal with these matrix effects. The matrix effects, mostly due to ion suppression, were shown to be a function of the DOC content and its origin. They were limited in soil water which presents low DOC content (-22% to +20%), thus internal quantification by isotopic dilution allowed their correction. On the contrary, in charged matrix they could rise up to the [-38% to -93%] range. The matrix effects variability between the samples suggested DOC content cut-offs above which sample purification was required. These cut-offs depended on compounds, with concentrations ranging from 30-290 mg C/L for antibiotics up to 600- 6400 mg C/L for the most apolar compounds. When necessary, a purification method compatible with fluoroquinolones and tetracyclines was furthermore proposed. It was based on a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) extraction procedure using a new composition of salts. The overall procedure was found simple, rapid, sensitive, accurate and efficient.