Determination of tissue-specific ion suppression by liquid extraction surface analysis mass spectrometry

Background: Liquid extraction surface analysis mass spectrometry (LESA-MS) is a promising approach for investigating the distribution of drugs and their metabolites in vivo. However, fundamental challenges concerning extraction efficiency and tissue specific ion suppression remain. In order to better understand these challenges, LESA-MS experiments using glyburide and an internal standard in rat tissue homogenates were performed. Methods: Dilutions of rat tissue homogenates were prepared and spiked with known concentrations of glyburide and d11-glyburide (internal standard). Samples for analysis were spotted on glass slides and dried. Liquid extraction surface analysis mass spectrometry experiments were performed using a Clarity (Advion, Inc., Ithaca, NY, USA) nanoelectrospray source coupled to a Sciex QTRAP 5500, (Concord, Ontario, Canada) triple quadrupole linear ion trap mass spectrometer operated in multiple-reaction monitoring (MRM) mode. Results: Linear regression yielded a calibration curve (r2 = 0.9999, n=3) and a lower limit of quantification of 1 ng/mL. Sample spot volume (2-5 µL) had no effect on range and reproducibility. Extraction efficiency from plasma was 1.7 ± 0.3%. Suppression of glyburide ionization in rat plasma and tissue homogenates was significant (P small intestine > liver > pancreas ≈ lung ≈ stomach ≈ kidney > brain. Conclusion: Extraction efficiency and matrix specific suppression of ionization are fundamental challenges surrounding liquid extraction surface analysis mass spectrometry. This work seeks to characterize these variables and to propose potential solutions such as integration of LESA-MS with liquid chromatography. Furthermore, these results suggest that LESA-MS has potential as a quantitative analytical technique