Evaluation of direct sample injection as a fast, no-sample handling, approach for the LC-MS/MS monitoring of pharmaceuticals in different water matrices

The determination of drug residues in water, particularly in environmental water, is a hot topic due to the usual presence of these emerging contaminants in the aquatic environment and their potential negative impact on water quality. The most widely approach applied at present for their determination is the use of a solid phase extraction (SPE) step followed by the LC-MS/MS measurement. This is due to the theoretical need to pre-concentrate the analytes and to produce “clean” sample extracts leading to less inferences in subsequent analysis. However, in LC-MS/MS based methods, the main interferences are not “visible” and are mostly due to matrix effects, which in fact are produced by unknown compounds that co-elute with the analytes and therefore not easily removed by SPE. As an alternative, an increasing trend is observed towards the use of direct injection (DI) of the samples, which is nowadays possible thank to the notable improvement in sensitivity of modern LC-MS/MS instrumentation. In this work, both approaches, SPE and DI, have been evaluated for the determination of 16 pharmaceuticals in three different types of water: groundwater, surface water and effluent wastewater. The study has been performed by using pharmaceutical reference standards and their corresponding isotope-labelled internal standards (ILIS) for efficient matrix effects correction. Both methodologies have been compared in terms of matrix effects, sensitivity, and suitability for the analysis of real-world water samples. Our data show that DI is an efficient alternative to SPE, with satisfactory analyte recoveries for most pharmaceuticals, matrix effects even lower than in SPE, and sufficient sensitivity for most of applications. In addition, the absence of sample treatment minimizes potential errors associated with this step, and there is a notable saving in the analysis time and costs. The analysis of Quality Control (QC) samples included in different sample batch sequences has been used to support the feasibility of using DI in this type of analysis.