An LC-MS/MS Method for Simultaneous Determination of the Toxic and Active Components of Cortex Periplocae in Rat Plasma and Application to a Pharmacokinetic Study.

Zhen Li,Yang Li,Jia Hao,Jun He,Jin Li,Rui Liu,Yan-Xu Chang

doi:10.1155/2019/1639619

Abstract

A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the toxic and other active components including isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract to rats. Plasma samples were prepared by protein precipitation with methanol. All compounds were separated on a C18 column with gradient elution using acetonitrile and formic acid aqueous solution (0.1%, v/v) as the mobile phase at a flow rate of 0.3 mL/min. The detection of all compounds was accomplished by multiple-reaction monitoring (MRM) in the positive electrospray ionization mode. The LC-MS/MS method exhibited good linearity for five analytes. The lower limit of quantification (LLOQ) was 0.48 ng/mL for scopoletin, periplogenin, and periplocymarin; 2.4 ng/mL for isovanillin and periplocin. The extraction recoveries of all compounds were more than 90% and the RSDs were below 10%. It was found that the absorption of scopoletin and periplocin was rapid in vivo after oral administration of cortex periplocae extract. Furthermore, periplocymarin possessed abundant plasma exposure. The results demonstrated that the validated method was efficiently applied for the pharmacokinetic studies of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract.

Highlights

Traditional Chinese Medicines (TCMs) play the vital roles in the prevention and treatment of diseases and are used in clinical practice for centuries in China [1]
Cortex periplocae was purchased from Shanxi province and the voucher specimen was deposited at Tianjin University of Traditional Chinese Medicine, Tianjin, China
The results showed that the dosage of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin was 32.76 mg/kg, 7.09 mg/kg, 28.89 mg/kg, 2.21 mg/kg, and 1.34 mg/kg, respectively

Summary

Introduction

Traditional Chinese Medicines (TCMs) play the vital roles in the prevention and treatment of diseases and are used in clinical practice for centuries in China [1]. In spite of their toxicity, these TCMs still were widely used in clinic due to their special pharmacological effects. It is worth noting that the clinical adverse reaction of the toxic TCMs limits their applications in clinical therapy. The safety of the toxic TCMs becomes increasingly important. Pharmacokinetic study was helpful for evaluating the safety by analyzing the absorption, distribution, metabolism, and excretion of drugs in vivo [1, 5]. It is essential to perform the pharmacokinetic study of the toxic and/or other active components in the toxic TCMs for achieving the best therapeutic effects and reducing the toxicity of TCMs [6, 7]

Methods

Results

Conclusion