Solid phase microextraction combined with thermal-desorption electrospray ionization mass spectrometry for...

Labor- and time-intensive sample preparation and liquid chromatography mass spectrometry (LC-MS) analysis are required for traditional pharmacokinetics (PK) studies. In order to simplify and accelerate the analytical process of the PK study, solid phase microextraction (SPME) combined with thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) was developed for rapid characterization of trace drug in biological fluids. Methylphenidate in plasma was extracted and concentrated by direct immersion SPME using fused-silica fibers coated with polydimethylsiloxane. The analytes on the SPME fiber were then characterized by TD-ESI/MS. Matrix-matched calibration with multiple reaction monitoring analysis was conducted to quantify methylphenidate. A linear calibration curve was constructed over a concentration range of 0.2-25 ng mL^-1 (r = 0.997). The quantitative results obtained by SPME-TD-ESI/MS were validated by LC-MS/MS. The average relative error for both methods was found to be -5.3%. As a viable alternative to LC-MS, SPME-TD-ESI/MS enables simple, rapid, and high-throughput analysis of drugs in plasma. The developed approach is particularly beneficial to PK studies for a very small sample volume (10 μL) is needed, the extraction time is as short as 3 min, and the detection time is less than 30 s.