# Recent Applications of Solid Phase Microextraction Coupled to Liquid Chromatography
## 2 Applications
### Technical Improvements  
Since the beginning, SPME has grown and evolved continuously, as demonstrated by the huge number of publications relating not only to its applications or to the search of new coatings and geometries, but also to experimental setups and novel coupling approaches. Many SPME-LC works have been recently published in the attempt to improve the performances of the whole SPME-LC analytical procedure.  
Back to 2010, the idea to use electrochemistry as a concentration approach led to the development of a method to electrochemically assist SPME extraction of parathion in water [71]. A pencil lead electrode simultaneously played the role of electrode and fiber. The extraction occurred with the application of a suitable reductive potential to the electrode/fiber. A static/dynamic desorption step was subsequently performed in the commercial SPME-LC desorption chamber, followed by LC-APCI-MS/MS analysis at trace levels.  
In the attempt to fasten the desorption process, a heated lab-made interface chamber was introduced by [PERSON] et al. and adopted in the development of a SPME-LC protocol for the determination of anticonvulsants in human plasma samples [72]. The method was fully validated and demonstrated to be adequate for therapeutic drug monitoring.  
Modifications on the SPME-LC interface and on the commercial PAN/C18 fiber assembly were also made by [PERSON] et al. [73], to avoid fiber coating damage and solvent/mobile phase leaks. The interface original tubes, replaced to minimize extra column volume, together with the optimized desorption and elution conditions, produced a good chromatographic efficiency. The system was tested by analyzing polycyclic aromatic hydrocarbons (PAH), proving to be robust and reliable.  
Analytes extracted by the SPME fibers from complex matrices were desorbed into solvent droplets in a digital microfluidics (DMF) device prior to LC-MS analysis in a further study [74] focused on the improvement of the desorption process. The brand new SPME-DMF approach was successfully applied to the sensitive determination of free steroids in urine. A relevant pre-concentration of the analytes was observed, due to the low volumes inherent to DMF, indicating the applicability of the device to the determination of different analytes in complex matrices at trace levels.  
A microfluidic open interface was designed and used to directly couple biocompatible SPME to tandem mass spectrometry [75]. Using this approach, the authors have optimized a rapid method for the determination of the antifibrinolytic drug tranexamic acid in patients undergoing cardiac surgery and experiencing renal disfunction, demonstrating the ability of this interface to perform an ultrafast monitoring of its concentration during administration (30 s per sample, 15 min with sample preparation) and then correcting the dosage in real time. A cross validation against a more conventional technique, such as standard thin film SPME-LC-MS/MS, confirmed the reliability of the procedure.  
[PERSON] et al. [76] proposed a modification of the commercial SPME-LC interface to perform both vibrations-assisted extraction and desorption, directly placing the fiber in the chamber usually dedicated to the desorption step. Extraction in dynamic mode was made by continuously supplying the sample matrix using a syringe, while a mixed static/dynamic mode was chosen for desorption. Selected PAH were determined in water samples at low concentration levels by LC with fluorescence detection and the results were found not significantly different from those obtained with the 550.1 EPA method.