Abstract

A sensitive and efficient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of gentiopicroside, geniposide, baicalin, and swertiamarin in rat plasma. To avoid the stress caused by restraint or anesthesia, a freely moving rat model was used to investigate the pharmacokinetics of herbal medicine after the administration of a traditional Chinese herbal prescription of Long-Dan-Xie-Gan-Tang (10 g/kg, p.o.). Analytes were separated by a C18 column with a gradient system of methanol–water containing 1 mM ammonium acetate with 0.1% formic acid. The linear ranges were 10–500 ng/mL for gentiopicroside, geniposide, and baicalin, and 5–250 ng/mL for swertiamarin in biological samples. The intra- and inter-day precision (relative standard deviation) ranged from 0.9% to 11.4% and 0.3% to 14.4%, respectively. The accuracy (relative error) was from −6.3% to 10.1% at all quality control levels. The analytical system provided adequate matrix effect and recovery with good precision and accuracy. The pharmacokinetic data demonstrated that the area under concentration-time curve (AUC) values of gentiopicroside, geniposide, baicalin, and swertiamarin were 1417 ± 83.8, 302 ± 25.8, 753 ± 86.2, and 2.5 ± 0.1 min µg/mL. The pharmacokinetic profiles provide constructive information for the dosage regimen of herbal medicine and also contribute to elucidate the absorption mechanism in herbal applications and pharmacological experiments.

Highlights

  • Long-Dan-Xie-Gan-Tang (LDXGT) is one of the best known traditional Chinese herbal prescriptions for the treatment of chronic hepatitis, jaundice, cystitis, and conjunctival congestion earache, as well as scrotum and extremitas inferior eczema [1,2]

  • To develop a sensitive and accurate analysis method for the determination of gentiopicroside, geniposide, baicalin, and swertiamarin, a triple quadruple mass spectrometer equipped with an electrospray ionization source is currently one of the most powerful tools for the simultaneous quantification of herbal components because of its high selectivity and sensitivity

  • Qualification analysis of a triple-quadrupole mass spectrometer operated in the multiple reaction monitoring (MRM) mode consisting of two parts: selecting the precursor ion (MS 1), and selecting a specific fragment of product ion (MS 2)

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Summary

Introduction

Long-Dan-Xie-Gan-Tang (LDXGT) is one of the best known traditional Chinese herbal prescriptions for the treatment of chronic hepatitis, jaundice, cystitis, and conjunctival congestion earache, as well as scrotum and extremitas inferior eczema [1,2]. Some of the components contained in the ingredient herbs, have been shown to have pharmacological properties. Several reports have indicated that gentiopicroside, geniposide, baicalin, and swertiamarin (the chemical structures are shown in Figure 1) have an important role in LDXGT.

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