UPLC-MS/MS method for determination of schisandrin in rat plasma and brain microdialysates: application to a comparative pharmacokinetic and brain distribution study in normal and Alzheimer’s disease rats

Abstract

Schisandrin is the major active ingredient of S. chinensis, which provides anti-AD activity. The objective of this study was to develop a method to study the comparative pharmacokinetics and brain distribution of schisandrin in normal and AD rats. Therefore, an efficient UPLC-MS/MS method for the determination of schisandrin in rat plasma and brain microdialysate has been developed and validated. The method showed good linearity over a wide concentration range (r > 0.99), and the obtained lower limit of quantification was 0.5 ng mL⁻¹ for the analyte in brain microdialysate samples. The intra-day and inter-day precision and accuracy of the analyte were well within acceptance criteria (±15%). The validated method has been successfully applied to comparing the pharmacokinetic and brain distribution profiles of schisandrin in normal and AD rat plasma and brain microdialysate. The results demonstrated that significant differences in the pharmacokinetic parameters of schisandrin were observed between the two groups, while the absorption of schisandrin in the AD group was significantly better than that in the normal group. The increase of schisandrin content in the brain provides a pharmacodynamic material basis for its anti-AD activity. The study will provide new ideas for the progression and development of AD therapy, and finding novel target drugs for AD therapy.