Yohimbine is a new erectile dysfunction compound derived from natural products, and its pharmacokinetic study is of great significance for its further development as a new drug.In this work, we developed a novel ZIF-8-based solid phase microextraction SPME-LC-MS/MS(Solidphasemicro extraction-liquid chromatography-mass spectrometry/mass spectrometry)method for the analysis of yohimbine in plasma and further for pharmacokinetic studies.The synthetic ZIF-8(zeolitic imidazolate frameworks-8) was used as the adsorbent for yohimbine microextraction, and the parameters affecting the extraction efficiency were systematically studied. Under optimal conditions, the SPME method based on pipette gun head showed excellent enrichment efficiency for yohimbine.A SPME -LC-MS/MS method for the determination of yohimbine in plasma samples was established. The linear range of the method is wide (0.3125-250ng/mL), and the R is 0.99063. By LC-MS/MS detection, the detection limit was as low as 0.104 ng/mL. Finally, the pharmacokinetics of Yohimbine were studied and compared with existing methods.