A critical review of bioanalytical and clinical applications of solid phase microextraction.

Studying the functions, mechanisms, and effects of drugs and other exogenous compounds on biological systems, together with investigations performed to understand biosystems better, comprises one of the most fascinating areas of research. Although classical sample preparation techniques are dominantly used to infer the relevant information from the investigated system, they fail to meet various imperative requirements, such as being environmentally friendly, applicable in-vivo, and compatible with online analysis. As a chameleon in the analytical toolbox, solid phase microextraction (SPME) is one of the best tools available for studying biological systems in unconventional ways. In this review, SPME is spotlighted, and its capability for bioanalytical applications, including drug analysis, untargeted and targeted metabolomics, in-vivo and clinical studies, is scrutinized based on studies reported in the past five years. In addition, novel extractive phases and instrumental coupling strategies developed to serve bioanalytical research are discussed to give the perspective for state-of-the-art and future developments. The literature assessment showed that SPME could act as a critical tool to investigate in-vivo biological systems and provide information about the elusive portion of the metabolome. Moreover, recently introduced miniaturized SPME probes further improved the low-invasive nature of the sampling and enabled sampling even from a single cell. The coupling of SPME directly to mass spectrometry significantly reduced the total analytical workflow and became one of the promising tools suitable for fast diagnostic purposes and drug analysis. The numerous applications and advancements reported in bioanalysis using SPME show that it will continue to be an indispensable technique in the future.