In situ-generated volumetric dried plasma spots for the analysis of edaravone and metabolites in animal models

In this study, for the first time rat plasma microsampling was carried out by means of in situ-generated volumetric dried plasma spot (vDPS) technology and applied to the determination of the neuroprotective agent edaravone and its sulphate and glucuronide metabolites. Sampling was performed using Telimmune® plasma separation cards (vPSC), which allow the formation of volumetrically accurate dried plasma spots (3 µL) from blood drops deposited on them. After accelerated forced drying and solvent extraction in methanol, drying and redissolution, analytes were baseline separated and quantified through an original HPLC-MS/MS analytical method. Validation assays provided excellent results, with detection limits between 0.7 and 1.7 ng/mL, and quantitation limits between 2.0 and 5.0 ng/mL. Extraction yields were higher than 81% and precision was lower than 14.1% (relative standard deviation, RSD). The volumetric microsampling approach offers much less invasive and stressful sampling. The vPSC technology offers a simple, cost-effective alternative method to produce a volumetric plasma sample that is stable when dried and eliminates transport. The developed analytical workflow appears suitable for advantageous application to pharmacokinetic and toxicokinetic animal studies of edaravone and its metabolites.