Achievements in robotic automation of solvent extraction and related approaches for bioanalysis of pharmaceuticals.

Currently, the growing demand on quick, easy and ecological sample pretreatment methods is unquestionable. Such challenge involves also approaches focusing on the analysis of pharmaceuticals and other endogenous compounds in biological matrices, termed as Bioanalysis. Solvent extraction such as liquid-liquid extraction (LLE), derived liquid phase microextraction (LPME) and related approaches such as solid liquid extraction (SLE), proved to be applicable in bioanalysis, as numerous papers have been published in this field. However, their manual performances may suffer from a long-term and laborious preparation, due to the inherent complexity of the biological samples. A high sample-throughput (enabling measurement of tens or hundreds of samples on a daily basis) can be achieved when automation of sample pretreatment is performed, resulting in decreased imprecision and low waste production of hazardous solvents and risky biological materials. Here, robotic systems have a key role, especially when multiple processing (e.g., 96-well plate format) and coupling to modern analytical instrumentation (e.g. LC-MS) are combined. A thorough overview on the up-to-date automations of LLE, LPME, SLE and solid LLE via robotics, is therefore presented. Pharmaceuticals and related compounds determined in classical liquid biological samples (i.e. plasma/serum, whole blood, urine, saliva etc.) and modern dried matrix spots (DMS) were considered as analytes of interest. The methodologies were critically compared to manual setups and among themselves.