Tailor-made deep eutectic solvents extraction combined with UPLC-MS/MS determination of icarrin and icarisid II in rat plasma and its comparative pharmacokinetic application.

Using green and high efficient solvents to extract and trace active ingredients of traditional Chinese medicine (TCM) in the complex biological samples was still challenging. In this paper, a co-friendly, fast pretreatment method with high extraction efficiency, based on the tailor-made deep eutectic solvent (DES) system, combined with ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination of icarrin and icarisid II in rat plasma samples, which can be further applied to comparative pharmacokinetic studies after oral administration of Herba Epimedii and icarrin monomer in rats, respectively. PrE (l-proline: ethylene glycol = 1:4 mol/mol) and acetonitrile were optimized and combined as the tailor-made DES at the volumetric ratio of 3:7 to extract icarrin and icarisid II, and to precipitate the protein in rat plasma in one step simultaneously. The extraction efficiency of the tailor-made DES was about 1.7 times of DES (PrE). The extraction recovery of icarrin and icarisid II in rat plasma samples by this method were within the range of 90-110 %, and the lower limits of quantification (LLOQ) were 0.32 ng mL-1 (icarrin) and 0.43 ng mL-1 (icarisid II). There was a linear relationship between 0.32-80.16 ng mL-1 (icarrin) and 0.43-107.4 ng mL-1 (icarisid II), which effectively reduced the detection limit. In this comparative pharmacokinetic study, the maximum plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC0-∞) of two analytes in rat plasma of Herba Epimedii group were both much higher than those in the icarrin monomer group, which suggested that other ingredients in Herba Epimedii may contribute to the in vivo absorption of icarrin and icarisid II. This simple, rapid, relatively green and high effeicient method would provide a new approach for the extraction of active ingredients from complex biological samples.