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Simultaneous determination of eight bioactive constituents of Zhi-Zi-Hou-Po Decoction in rat plasma by ultra-high performance liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study.

J Sep Sci. 2019 Oct 21;:

Authors: Zhu H, Guan J, Shi J, Pan X, Chang S, Zhang T, Feng B, Gu J

Abstract
Zhi-Zi-Hou-Po Decoction, consisting of Gardenia jasminoides Ellis, Magnolia officinalis Rehd. et Wils. and Citrus aurantium L, is a classical Traditional Chinese Medicine formula for the treatment of depression in China for thousands of years. In order to make good and rational use of this formula in the future, a sensitive, selective and reliable ultra-high performance liquid chromatography-tandem mass spectrometry method was developed for simultaneous determination of two iridoid glycosides (geniposide and genipin gentiobioside), two lignans (honokiol and magnolol), four flavonoid glycosides (isonaringin, naringin, hesperidin and neohesperidin), the major bioactive constituents of Zhi-Zi-Hou-Po Decoction, in rat plasma using paeoniflorin as internal standard. Plasma samples were pretreated by a simple protein precipitation with acetonitrile. Chromatographic separation was performed on a shim-pack XR-ODS C18 column (75 mm × 3.0 mm, 2.2 µ;m) using gradient elution with mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.5 mL/min. Mass spectrometric detection was conducted on a 3200 QTRAP mass spectrometry equipped with electrospray ionization source in negative ionization mode. Quantification was performed using multiple reactions monitoring mode. Calibration curves exhibited good linearity (r > 0.9947) over a wide concentration range for all analytes, and the lower limit of quantification were 10, 5, 1, 5, 1, 5, 1 and 5 ng/mL for geniposide, genipin gentiobioside, honokiol, magnolol, isonaringin, naringin, hesperidin and neohesperidin, respectively. The intra-day and inter-day precisions at three quality control levels were less than 12.3% and the accuracies ranged from -11.2% to 10.7%. Extraction recovery, matrix effect and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of the eight analytes after oral administration of Zhi-Zi-Hou-Po Decoction to rats. This article is protected by copyright. All rights reserved.

PMID: 31633862 [PubMed – as supplied by publisher]

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