Instantaneous monitoring of free sarin in whole blood by dry blood spot–thermal desorption–GC–FPD/MS analysis

Dry blood spot (DBS), a micro whole-blood sampling technique, enables rapid and self-blood collection; it is stable and economical. Currently, DBS filters require various sample preparation procedures specifically tailored for the target compounds, which are followed by GC–MS or LC–MS analysis. However, the small amounts of blood make the approach analytically challenging, mostly in terms of sensitivity and quantification. Herein, we introduce a new DBS concept for GC-compatible volatile to semi-volatile compounds in which DBS is directly coupled with thermal desorption analysis, thus eliminating time consuming treatments. Furthermore, to stabilize the target compound over the sampling DBS substrate, a commercial filter based on an extremely efficient trapping adsorption phase, styrene–divinylbenzene (SDVB), is first used. The performance of the new SDVB–DBS concept was demonstrated herein for monitoring the most volatile chemical warfare agent, sarin, which might be present in blood and the detection of which is usually challenging due to its rapid metabolism. This study encompasses adequate sampling and analysis method parametrization and validation, leading to a detection sensitivity of 100 pg sarin per 30 µL whole blood in 5-day-old samples, with a linear dynamic range of two orders of magnitude, adequate precision, and acceptable accuracy. Applying the method to an in-vivo mouse intranasal exposure experiment (3LD50 GB) enabled the successful detection of 25–90 ng mL−1 free sarin in blood samples drawn 2 min after exposure. The method’s performance clearly emphasizes the potential of the new concept in “freezing the clock” for reactive whole blood media in pharmacokinetics and pharmacodynamics studies, as well as in applications in which informative and reliable monitoring of unstable target compounds and biomarkers is desired.