Abstract: AIM: To establish a method that combine dried plasma spots and LC-MS/MS for simultaneous determination geniposide, shanzhiside and genipin geniobioside in dog plasma and study pharmacokinetic in dogs. METHODS: Chromatographic separation was achieved on an Ecosil C₁₈ (4.6 mm×150 mm,5 μm) column and the mobile phase consisting of methanol and 20 mmol/L ammonium formate (containing 0.1% formic acid), gradient elution. An electrospray ionization (ESI) source was applied and operated in the positive multiple reaction monitoring (MRM) mode. Using dried plasma spots technology collect plasma samples after intravenous administration of Zhizi. The assay employed simple solvent extraction and sonication of the DPS sample, followed by LC-MS/MS system for analysis. RESULTS: Good linearity was achieved for the three compounds (r>0.99), the intra-day and inter-day precision(RSDs) were below 15%, the absolute recoveries were between 79.9%-91.4%. The main pharmacokinetic parameters of geniposide, shanzhiside, genipin geniobioside as follows: the t_1/2 were 6.86,0.687,2.11 h , the AUC0→t were 158,9.16,34.0 μg·mL^-1·h.CONCLUSION: The developed LC-MS/MS method is sensitive and specific for simultaneous determination of geniposide, shanzhiside and genipin geniobioside in dried plasma spots .The dried plasma spots were stable at room temperature, easy transportation and preservation,and it can be used for pharmacokinetic research.

Key words: dried plasma spot, LC-MS-MS, iridoid glycosides, pharmacokinetic