Direct coupling of solid phase microextraction with electrospray ionization mass spectrometry: A Case study for detection of ketamine in urine

Abstract Electrospray ionization mass spectrometry (ESI-MS) is a commonly used technique for analysis of various samples. Solid phase microextraction (SPME) is a simple and efficient technique that combines both sampling and sample preparation into one consolidated step, preconcentrating extracted analytes for ultra-sensitive analysis. Historically, SPME has been coupled with chromatography-based techniques for sample separation prior to analysis, however more recently, the chromatographic step has been omitted, with the SPME device directly coupled with the mass spectrometer. In this study, direct coupling of SPME with ESI-MS was developed, and extensively validated to quantitate ketamine from human urine, employing a practical experimental workflow and no extensive hardware modification to the equipment. Among the different fibers evaluated, SPME device coated with C 18 /benzenesulfonic acid particles was selected for the analysis due to its good selectivity and signal response. Different approaches, including desorption spray, dripping, desorption ESI and nano-ESI were attempted for elution and ionization of the analytes extracted using the SPME fibers. The results showed that the desorption spray and nano-ESI methods offered better signal response and signal duration than the others that were evaluated. The analytical performance of the SPME-nano-ESI-MS setup was excellent, including limit of detection (LOD) of 0.027 ng/mL, limit of quantitation (LOQ) of 0.1 ng/mL, linear range of 0.1–500.0 ng/mL (R 2  = 0.9995) and recoveries of 90.8–109.4% with RSD 3.4–10.6% for three validation points at 4.0, 40.0 and 400.0 ng/mL, far better than the performance of conventional methods. The results herein presented, demonstrated that the direct coupling of SPME fibers with ESI-MS-based systems allowed for the simple and ultra-sensitive determination of analytes from raw samples such as human urine.