1. Academic Validation
  2. Simultaneous determination of two iridoid glycosides, two anthraquinones and four flavonoid glycosides of Zhi-Zi-Da-Huang decoction in rat plasma by UFLC-MS/MS: application to a comparative pharmacokinetic study in normal and cholestatic liver injury rats

Simultaneous determination of two iridoid glycosides, two anthraquinones and four flavonoid glycosides of Zhi-Zi-Da-Huang decoction in rat plasma by UFLC-MS/MS: application to a comparative pharmacokinetic study in normal and cholestatic liver injury rats

  • J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jun 1;960:116-25. doi: 10.1016/j.jchromb.2014.04.031.
Heyun Zhu 1 Kaishun Bi 2 Fei Han 2 Jiao Guan 1 Zheng Tang 2 Kelin Chen 2 Longshan Zhao 2 Qing Li 2 Ran Yin 3 Xiaohong Hou 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China; School of Pharmacy, Jilin Medical College, 5 Jilin Street, Fengman District, Jilin 132013, China.
  • 2 School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
  • 3 School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: yinran_syphu@163.com.
  • 4 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: houxiaohong@syphu.edu.cn.
Abstract

A selective, sensitive and reliable ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed for the simultaneous determination of two iridoid glycosides (geniposide and genipin gentiobioside), two Anthraquinones (rhein and emodin) and four flavonoid glycosides (isonaringin, naringin, hesperidin and neohesperidin), the major active ingredients of Zhi-Zi-Da-Huang decoction (ZZDHD), in rat plasma using paeoniflorin as internal standard (IS). After liquid-liquid extraction with ethyl acetate-isopropanol (1:1, v/v), separation was achieved on a Shim-pack XR-ODS C18 column (75 mm×3.0 mm, 2.2 μm) using gradient elution with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.4 mL/min. Detection was performed on 4000 QTRAP mass spectrometry equipped with turbo ion spray source in the negative ionization and multiple reaction monitoring (MRM) mode. The intra- and inter-day precisions (as relative standard deviation) were less than 11.4%, and accuracy (as relative error) was within ± 10.0%. The lower limits of quantification (LLOQ) were 4.0, 0.5, 2.0, 0.1, 1.0, 2.0, 1.0, 2.0 ng/mL for geniposide, genipin gentiobioside, rhein, emodin, isonaringin, naringin, hesperidin and neohesperidin, respectively. The extraction recoveries of the analytes and IS from rat plasma were all more than 86.0%. The method was fully validated and applied to compare the pharmacokinetic profiles of the analytes in normal and cholestatic liver injury (CLI) rats after oral administration of ZZDHD. Results showed that there were remarkable differences in pharmacokinetic properties of the analytes between normal and CLI group.

Keywords

Cholestatic liver injury; Pharmacokinetics; Rat plasma; UFLC-MS/MS; Zhi-Zi-Da-Huang decoction.

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