Strategies for the Direct Coupling of Solid Phase Microextraction to Mass Spectrometry

Abstract

In recent years, advances in direct sample to mass spectrometry (MS) techniques have allowed for the application of these methods towards quantitative analysis in complex matrices such as biofluids and tissue. However, the predictable limitations of these technologies, such as ionization suppression, poor sensitivity at trace levels, and narrow linear dynamic range, have been the driving force toward the development of methods that efficiently integrate sampling, sample cleanup, and analyte collection and ionization. In this context, the direct interface of microextraction technologies and MS has undoubtedly revolutionized the speed, efficacy, and robustness with which complex matrices can be scrutinized. In this thesis, numerous strategies recently developed for the direct and efficient coupling of Solid Phase Micro Extraction (SPME) and MS are presented towards the analysis of complex matrices. Aiming to supply a range of technologies suited for diverse applications, different SPME geometries such as coated fibers, blades and meshes, as well as ionization approaches, such as atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI), were studied. In addition, these workflows are compatible with SPME devices that undergo either sampling of tissue or direct immersion into liquid samples. The strategies developed as part of this doctoral dissertation include the following: SPME-Transmission Mode coupled to MS via Direct Analysis in Real Time (SPME-TM-DART-MS), SPME coupled to MS via nano-ESI (SPME-nanoESI-MS), SPME coupled to MS via Open Port Probe (SPME-OPP-MS), and Coated Blade Spray-MS (CBS-MS). In most of the applications herein compiled, total analysis time does not exceed 5 minutes, while sample volumes ranging between 1 and 1500 μL can be utilized for analysis. Sampling/sample-preparation is performed either by spotting the sample onto the SPME device, or by immersing the SPME device on a vessel containing the sample. Despite short extraction times, limits of detection in the pg/mL to sub-ng/mL range were obtained, while good accuracy (i.e. 80-120%) and linearity (i.e. ppt to ppm) were attained for all studied probes (i.e. therapeutic drugs, drugs of abuse, pharmaceuticals, and pesticides) in the diverse sample matrices (e.g. phosphate buffer saline, urine, plasma, blood, grape juice, orange juice, milk, and ground water). Lastly, this work describes exemplary cases in which the mere coupling of SPME to MS is not sufficient to answer relevant analytical questions, and the use of a chromatographic step is justified. Hence, supplementary instrumental strategies that allow for removal of co-extracted interferences or source artifacts, such as Differential Mobility Spectrometry (DMS), tandem MS in time (MSn), and Multiple Reaction Monitoring with Multistage Fragmentation (MRM3), are also discussed in this dissertation. Although the body of this work is chiefly focused on biofluid analysis, the attained results certainly support the implementation of this group of technologies towards the analysis of diverse complex matrices of environmental, biological, food, clinical, military, forensic, and pharmaceutical significance. We are confident that in a foreseeable future, this work will encourage readers around the globe towards the use of SPME-MS as a workhorse for on-site and benchtop analysis. In few words, SPME-MS technologies appear poised to shift the paradigm of direct sample introduction to MS.