Abstract

Chaihu-shugan-san (CHSGS) has been widely used in China to treat depression and gastrointestinal diseases for thousands of years, but little is known about its pharmacokinetic properties. The purpose of our study is to develop a reliable and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to detect five components in beagle plasma and study their pharmacokinetic after oral administration of CHSGS in beagles. An Agilent C18 column (2.1 × 150 mm, 3.5 μm) was used to separate the analytes, and the column temperature was maintained at 40°C. A gradient elution procedure was used with solvent A (acetonitrile) and solvent B (0.1% formic acid, aqueous) as mobile phases. The elution procedure was 60% B—10% B (0–3 min) and 10% B—60% B (3.1–4 min). The flow rate was 0.3 mL/min, and the total measurement time was 4 min. Within the determined range, the standard calibration curves of the five analytes had a satisfactory linear relationship (r2 ≥ 0.9923). The recovery rate (n = 6) of the five analytes was between 85.42% and 90.85%, and the matrix effects (n = 6) were between 94.52% and 103.91%. These results show that the validated method could be successfully applied to study the pharmacokinetic in beagles after a single dose of CHSGS.

Highlights

  • Chaihu-shugan-san (CHSGS), a classic prescription of traditional Chinese medicine (TCM), is derived from the Book of Jingyue and recorded in the China Pharmacopoeia (2015 edition) [1]

  • An efficient, simple, and sensitive HPLC-MS/MS method was established for the first time to simultaneously detect naringin, neohesperidin, hesperidin, paeoniflorin, and liquiritin

  • To verify the specificity of the experimental method, three groups of blood samples were analyzed by HPLC-MS/ MS: (a) six individual beagle blank plasma samples; (b) plasma samples added with all analytes and internal standard (IS); and (c) real plasma samples after giving a single dose of CHSGS

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Summary

Introduction

Chaihu-shugan-san (CHSGS), a classic prescription of traditional Chinese medicine (TCM), is derived from the Book of Jingyue and recorded in the China Pharmacopoeia (2015 edition) [1]. Naringin and neohesperidin are two major active ingredients in Zhi-qiao, which are one of the antidepressant mechanisms of CHSGS [10]. To improve the development of CHSGS, comprehensive studies of CHSGS are required and a validated bioanalytical method is necessary to support some pharmacokinetic researches. In this experiment, an efficient, simple, and sensitive HPLC-MS/MS method was established for the first time to simultaneously detect naringin, neohesperidin, hesperidin, paeoniflorin, and liquiritin. An efficient, simple, and sensitive HPLC-MS/MS method was established for the first time to simultaneously detect naringin, neohesperidin, hesperidin, paeoniflorin, and liquiritin This validated method was first successfully applied to a pharmacokinetic study of CHSGS in beagles

Materials and Methods
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