Microdialysis combined with UPLC–MS/MS method for determination of tetramethylpyrazine and ferulic acid in striatum of awake and anesthetic rats subjected to cerebral ischemia

Simultaneous determination and pharmacokinetic investigation of tetramethylpyrazine and Ferulic acid in striatum of awake and anesthetic rats. [Display omitted] •We establish UPLC–MS method for detection of TMP and FA in rat brain microdialysates.•Microdialysis is applied to research brain pharmacokinetics of FA and TMP.•We investigate the effect of co-administration on the PK parameters of drugs.•We research the effect of different levels of anesthesia on the drug PK parameters.•Co-administration and the waking state can improve the bioavailability of TMP. A rapid, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method has been developed for the simultaneous determination and pharmacokinetic investigation of Tetramethylpyrazine (TMP) and Ferulic acid (FA) in rat striatum. The method was validated over the concentration range of 1.15–505ng/mL for TMP and 3.23–101ng/mL for FA, with a lower limit of quantitation (LLOQ) of 1.15ng/mL and 3.23ng/mL, respectively. This method can be successfully applied in pharmacokinetic studies of TMP and FA in striatum of awake and anesthetic rats. The cerebral blood flow velocity (CBF) during middle cerebral artery occlusion (MCAO) was monitored by Laser speckle contrast imaging, to observe whether the compatibility of TMP and FA could improve CBF against cerebral ischemia/reperfusion (I/R) injury. Infarct volume was examined to evaluate severity of ischemic brain injury. The pharmacokinetic study indicated that T1/2, Cmax, MRT and AUC0-inf were changed after combined administration of TMP and FA, when compared with either drug alone both in awake and anesthetic groups. The pharmacodynamics results showed that co-administration of drugs could enhance the CBF during middle cerebral artery occlusion and reduced the infarct volume. Taken together, the compatibility treatment of TMP and FA might be a promising therapeutic strategy for ischemic stroke. Further study is required to optimize the compatibility proportion.