Rapid drug detection in whole blood droplets using a desorption electrospray ionization static profiling approach – a proof‐of‐concept

Abstract

Rationale The introduction of desorption electrospray ionization (DESI) – and ambient desorption/ionization (ADI) ion sources in general – in the 2000s has opened new possibilities for mass spectrometric (MS) analyses of biological sample surfaces. DESI allows for a rapid screening of solid samples because no sample preparation is needed and the analysis is performed at atmospheric pressure. In the present study, we used DESI as an ion source for the rapid detection of a small molecule in blood droplets deposited on glass slides. Methods Blood was spiked with different concentrations of a model drug, mebendazole. One microliter blood droplets of each preparation were deposited on the surface of a glass slide and analyzed by DESI, either in imaging or profiling mode. Results The results suggested that DESI imaging mode was not appropriate for the detection of mebendazole in blood droplets as an initial solvation time was necessary before the obtention of signal. A profiling approach consisting of analyzing a single position of the blood droplet was used for further analysis and allowed mebendazole to be detected in the fg range and to monitor the volume of sample analyzed. Conclusions The study suggests that profiling mode at a single position is adequate for DESI analyses in whole blood droplets. This proof‐of‐concept study illustrates the potential of DESI profiling as a possible alternative to liquid chromatography/MS analyses of whole blood, when analyses are needed within a restricted time. Rapid detection methods in blood at atmospheric pressure may find interesting applications in the fields of toxicology and pharmacology.

Approaching sites of action of drugs in clinical pharmacology: New analytical options and their challenges

“…One of our recent ultraperformance LC‐MS/MS assays suggests that femtomolar concentrations of midazolam can be analysed with attomoles injected for the analyses 133 . Our group could directly detect small molecules from blood droplets in the femtogram range 134 . Therefore, minute compound amounts can be found from samples analysed from surfaces.…”

“…133 Our group could directly detect small molecules from blood droplets in the femtogram range. 134 Therefore, minute compound amounts can be found from samples analysed from surfaces. High-sensitivity devices would allow quantifying drugs in cells using the MALDI imaging mode The link between on-surface sampling and liquid handling is laser microdissection (LMD), which allows for the precise collection of solid samples deposited on surfaces.…”

Important Requirements for the Selection of Internal Standards during the Development of Desorption/Ionization Assays for Drug Quantification in Biological Matrices—A Practical Example

“…These advantages include the rapidity of sample preparation and analysis from any biological matrix, including fluids [ 3 , 4 , 5 , 6 , 7 , 8 ], and the ability to quantify drugs in their histological context when tissue sections are used [ 1 , 9 , 10 ]. Our group has previously shown that the surface properties of the biological matrix in desorption electrospray ionization (DESI) [ 11 ] or the matrix crystallization effects in matrix-assisted laser desorption/ionization (MALDI) [ 2 , 12 ] can strongly affect signal stability compared to electrospray ionization (ESI). For this reason, reliable normalization using appropriate internal standards (IS) is a crucial step for the successful development of fully validated methods according to regulatory guidelines [ 2 ].…”

Direct multiclass desorption electrospray ionization–tandem mass spectrometry method for the analysis of sleep inducers and ototoxic drugs in dried blood spots

“…Surprisingly, during the period covered from the appearance of DESI to now, only a few projects have been devoted to direct analysis of DBS with DESI. The first ones were a sort of preview of the interface potential 13,14 while, in the subsequent decade, there were only two quantitative methods for whole blood, 15,16 one on plasma 17 and a proof of concept 18 . Other projects involved sample pretreatments such as solid‐phase extraction or thin liquid membrane extraction 19,20 …”