Direct Ionization of Solid-Phase Microextraction Fibers for Quantitative Drug Bioanalysis: From Peripheral Circulation to Mass Spectrometry Detection

Abstract

A novel approach is described for the quantitative bioanalysis of drugs in blood samples by ionization of the analytes collected on solid-phase microextraction (SPME) fibers by mass spectrometry (MS). The technique combines the attractive features of SPME microsampling using minimal sample volumes with the speed, selectivity, and sensitivity capabilities of MS detection. The method reported in this study involved generating gas-phase ions directly from SPME fibers without the need for any additional sample preparation or chromatographic separation; the entire process was completed within 5 min. Traditionally, analytes extracted by SPME fibers are desorbed by washing with suitable solvents followed by a transfer into a sample vial and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to quantify the amount of analyte extracted and thereby determining the analyte concentration in the matrix. These sample preparation steps are completely eliminated by inserting the SPME fiber directly into the MS. Physiologically relevant concentrations of metoprolol and propranolol in blood samples were measured over several orders of magnitude down to concentration levels of 10 ng/mL. This preliminary assessment of direct SPME-MS showed high sensitivity (ng/mL), acceptable reproducibility (<30%), and lack of carryover. This novel approach simplifies current bioanalytical procedures providing time and cost savings. It demonstrates considerable potential for qualitative and quantitative pharmaceutical bioanalysis as well as other areas of challenging environmental and food analysis.

Direct Coupling of Solid-Phase Microextraction with Mass Spectrometry: Sub-pg/g Sensitivity Achieved Using a Dielectric Barrier Discharge Ionization Source

“…The same authors reported the use of coated-blade SPME devices, from which the analytes were electrosprayed [21]. Other approaches are based on SPME-DESI-MS [22] and solvent-assisted spray-based SPME-MS [23]. Recently, another SPME-LTP-MS coupling was reported [24].…”

Application of solid‐phase microextraction in current biomedical research

“…Ahmad et al. developed a method for the quantitative bioanalysis of two beta‐blockers, metoprolol and propranolol, in blood samples by inserting C18 fiber directly into the MS . In an attempt to mimic the intravenous blood flow in a living organism, the SPME fibers were exposed to blood samples with 500 rpm agitation.…”

Quantitative mass spectrometry methods for pharmaceutical analysis

“…Therefore, solid-phase micro-extraction (SPME) is used more and more frequently [121]. Because of the smaller sample volumes required and its reduced solvent consumption, lower cost and high-performance characteristics, SPME is also very suitable for the analysis of biological samples [51,122]. A detailed summary of key features of SPME, SPE and LLE can be found in Boyaci et al [123].…”