# Recent Applications of Solid Phase Microextraction Coupled to Liquid Chromatography
## 1 Introduction  
The demand for modern, sensitive, and accurate analytical methods for the determination of compounds at low concentration levels in complex matrices, such as biological, food, and environmental, is always increasing. The main steps of an analytical process are sampling, sample preparation, instrumental analysis, and data processing, and any of them may deeply affect the analytical performance. Today, analytical instrumentation has reached an advanced level of technology and performances unimaginable until a few years ago, that allow selective and sensitive analytes determination even in complex extracts. On the other hand, sample preparation is usually the major source of inaccuracy and imprecision on analysis and remains a critical and time-consuming component of the workflow. It is devoted to the transfer of analytes from sample matrices to simplified final extracts compatible with the analytical instrument to be employed and is certainly a prerequisite for the attainment of reliable results. Consequently, any improvement on chemical analysis greatly depends also on the technological advances of modern sample preparation techniques. Solid phase microextraction (SPME) is an evolving technique for the extraction of organic compounds from gaseous, aqueous, and solid matrices. The principle of SPME involves the equilibration of the analytes between a polymeric phase, generally coated onto a fiber, and the sample matrix. It has numerous advantages over other sample preparation techniques such as liquid-liquid (LLE), solid-phase (SPE), and supercritical fluid extraction (SFE), i.e., rapidity, low cost, ease of use and automation, and ability to perform in situ measurements. Furthermore, no harmful solvents are needed. Since its introduction [1], many variants of the SPME technique have evolved and it can be found in different geometries, in particular in-tube [2], hollow fiber [3], thin-film [4], coated-tip [5], and magnetic nanoparticles [6]. However, the fiber geometry, where a fiber iscovered by a specific sorbent to extract target compounds from the sample matrix by direct immersion (DI-SPME) or from the headspace (HS-SPME) [7], remains the most widespread. Fiber SPME has been widely used in combination with various analytical techniques: gas and liquid chromatography (GC, LC) [8; 9; 10; 11; 12], capillary electrophoresis (CE) [13], mass spectrometry (MS) [10; 11; 12], inductively coupled plasma MS (ICP-MS) [14], and ICP-optical emission spectrometry (ICP-OES) [15]. However, most applications have been performed with gas chromatography (GC) and, to a lesser extent, liquid chromatography (LC). Of course, SPME-GC applications are limited to the analysis of volatile and thermally stable compounds, while SPME-LC can be used for the analysis of thermally labile compounds with poor volatility. Nevertheless, for many years, most efforts towards applications and practical implementations of SPME have privileged coupling with GC. The main reason for that is the different nature between the desorption steps used in LC and GC. In fact, solid phase microextraction devices are easily interfaced with GC injectors since the thermal desorption process follows the same steps used for standard GC injections. On the contrary, the SPME-LC coupling requires a slower liquid desorption process, due to slower diffusion kinetics. Desorption is generally performed off-line, in a vial, or on-line, in the chamber of a dedicated interface, using two different modes: in the flowing mobile phase (dynamic mode) or in an appropriate solvent mixture for a specific time before injection is performed (static mode). Furthermore, the on-line liquid desorption process must be carefully optimized to avoid the decrease of the chromatographic efficiency. Despite the problems, SPME-LC has gained a good degree of popularity over the years, as demonstrated by dedicated articles that have extensively reviewed its state of the art in the past [8; 9].