Application of a Liquid Extraction Based Sealing Surface Sampling Probe for Mass Spectrometric Analysis of Dried Blood Spots and Mouse Whole-Body Thin Tissue Sections

Abstract

The utility of a liquid extraction based sealing surface sampling probe (SSSP) for the direct mass spectrometric analysis of targeted drugs and metabolites in dried blood spots (DBSs) and whole mouse thin tissue sections was demonstrated. The accuracy and precision for the quantitative analysis of a minimum of 50 ng/mL sitamaquine or acetaminophen in DBSs on paper were well within the required 15% dictated by internationally recognized acceptance criteria for assay validations. Analysis of whole-body mouse thin tissue sections from animals dosed with propranolol, adhered to an adhesive tape substrate, provided semiquantitative information for propranolol and its hydroxyproranolol glucuronide metabolite within specific organs of the tissue. The relative abundances recorded for the two compounds in the brain, lung, kidney, and liver were in nominal agreement with previously reported amounts based on analysis using a liquid microjunction surface sampling probe (LMJ-SSP), whole-body autoradiography (WBA), and high-pressure liquid chromatography-mass spectrometry (HPLC-MS). The ability to sample and analyze from tape-adhered tissue samples, which are generally employed in WBA analysis, presents the possibility of consecutive WBA and SSSP-MS analysis of the same tissue section. This would facilitate assignment, and possibly quantitation, of the different molecular forms of total drug related material detected in the WBA analysis. The flexibility to sample larger or smaller spot sizes, alternative probe sealing mechanisms, and a reduction in internal volumes and associated sample carryover issues will be among the first simple improvements necessary to make the SSSP-MS method a practical DBS and/or thin tissue section analysis tool or to expand its use to other surface sampling applications.