On-line SPE-LC-MS/MS analysis of wide-range polarity pharmaceutical compounds in aqueous matrices: problems and solutions

Modern environmental analytical chemistry must deal with the increasing demand of high-throughput analysis. Furthermore, the environmental monitoring of organic micropollutants in water samples is a fairly laborious issue, due to a number of reasons, such as the need of the simultaneous determination of a very high number of compounds, frequently characterized by a wide range of physicochemical properties and capable to exert negative effects on the environment, even at very low concentrations (i.e. parts per billion-trillion levels). All these issues can be faced using on-line solid phase extraction coupled to tandem mass spectrometric detection (on-line SPE-LC-MS/MS), which has been successfully applied to the monitoring of several classes of organic micropollutants in various aqueous matrices. Pharmaceutical compounds in aqueous matrices are matter of environmental concern owing to their widespread use, continuous release, persistence, and increasing evidence for their ecotoxicological effects. Pharmaceuticals are excreted either as such or as metabolites after human administration and via the sewage system they reach wastewater treatment plants (WWTPs) where they are often inefficiently removed, thus being discharged into the receiving water bodies. Pharmaceuticals represent a group of substances characterized by the presence of acid and/or basic functionalities and a very wide range of polarity, thus representing a challenge for the analytical chemist when a multiresidual determination is required. In this work, the applicability of the on-line SPE-LC-MS/MS approach to the determination of a number of pharmaceutical compounds characterized by very different physicochemical properties was investigated. Antibiotics, beta-blockers and anti-inflammatory drugs most used in Italy were selected according to the reports of the Italian Medicine Agency, together with some metabolites. Different SPE sorbents, such as the poly(divinylbenzene-co-N-vinylpyrrolidone) (PVB-VP) and PVB-VP functionalized with a weak cation exchange group, and stationary phases (e.g. octadecylsilane and pentafluorophenyl silane) were tested. Under the best experimental conditions, recoveries included in between 40 and 120% were obtained on MilliQ water. Apparent recoveries significantly differed from these values, mainly due to matrix effects within the ionization process. Detection limits were however included from sub-ng/L to tens of ng/L, depending on the compound and sample analysed. The overall analysis time per sample was about 25 minutes. The analysis of various effluent WWTP samples evidenced the presence of several pharmaceuticals and especially antibiotics and beta-blockers, at concentrations as high as tens of μg per litre.