Miniaturized SPME tips directly coupled to mass spectrometry for targeted determination and untargeted profiling of small samples.

The analysis of small sample volumes, such as biofluids, tissues, and cells, has become increasingly popular over the past few years. In this paper, we introduce a sample-preparation tool that is suitable for such analysis, namely, a solid-phase microextraction (SPME) minitip featuring a tip apex (1 mm) that is coated with biocompatible polyacrylonitrile (PAN) and N-vinylpyrrolidone-co-divinylbenzene, also known as HLB particles. HLB particles are suitable for extracting a wide range of compounds with varying polarities, and the proposed SPME minitips were successfully used for the targeted (MS/MS) quantitation of polar, semi-polar, and nonpolar drugs of abuse (DoAs) in 1 µL of blood via offline nanoelectrospray ionization (nESI). Low limits of detection (LOD) and quantification (LOQ) were obtained for most of the targeted analytes (i.e. LODs between 0.5 and 2.5 ng mL). In addition, untargeted metabolomic profiling was performed on a single caviar egg (diameter ≤2.9 mm), with analysis being conducted via liquid chromatography high-resolution mass spectrometry (LC/HRMS). Clear chromatographic peaks were obtained despite the small size of the caviar eggs and the dilution introduced by LC. Multidimensional statistical analysis (PCA & PLS-DA) showed that the SPME minitips were able to successfully discriminate between samples, and the compounds that were tentatively identified corresponded with those expected to be found in fish. These findings highlight the importance of using suitable materials for pre-concentrating probe-sampling approaches, as they can provide analysts with sensitive instrumental response, particularly when studying the chemical profiles of small organisms.