1. Simultaneous determination of multiple compounds of Da-Huang-Xiao-Shi decoction in rat plasma by LC-MS/MS and its application in a pharmacokinetic study.
- Author
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Jin, Jingyi, Xue, Haoyu, Sun, Xiaoshu, Zan, Bin, Li, Yuanyuan, Wang, Tianming, Shi, Rong, and Ma, Yueming
- Subjects
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EMODIN , *MATRIX effect , *RATS , *FORMIC acid , *BIOACTIVE compounds , *ACETIC acid - Abstract
• A novel LC–MS/MS method for bioanalysis of Da-Huang-Xiao-Shi decoction (DHXSD). • Multiple compounds of DHXSD were simultaneously monitored in plasma. • Monitoring 13 prototypes and their glucuronide/sulfate metabolites. • Challenge of structual diversity and various linear ranges of compounds was overcome. • The pharmacokinetic characteristics of DHXSD were studied for the first time Da-Huang-Xiao-Shi decoction (DHXSD), a traditional Chinese medicinal formula, has been used mainly to treat jaundice for more than 1700 years in China. In this study, we developed a rapid, sensitive, and accurate LC–MS/MS method to simultaneously determine multiple, potentially bioactive compounds of DHXSD, including five alkaloids (berberine, phellodendrine, palmatine, jatrorrhizine, and magnoflorine), five anthraquinones (rhein, aloe-emodin, emodin, chrysophanol, and physcion), two iridoid glycosides (geniposide and genipin 1-gentiobioside), and one iridoid aglycone (genipin) in rat plasma. Plasma samples collected from rats were treated immediately with 5% acetic acid to avoid the degradation of genipin. After protein precipitation with acetonitrile containing 5% acetic acid, the compounds were reconstituted in acetonitrile–water (50:50, v/v) solution containing 6.5% formic acid and separated on the ACQUITY™ UPLC BEH C 18 column (2.1 × 100 mm; 1.7 μm) using a mobile phase composed of 2 mM ammonium formate in water (solvent A) and acetonitrile (solvent B) at a flow rate of 0.3 mL/min. Quantitation was performed on a Triple Quand 5500 tandem mass spectrometer coupled with an electrospray ionization (ESI) source. Multiple reaction monitoring (MRM) was used to quantify compounds in positive and negative ion modes. The method validation results showed that the specificity, linearity, precision and accuracy, recovery, matrix effect, and stability of the 13 compounds met the requirements for their quantitation in biological samples. This newly established method was successfully used in a pharmacokinetic study on rats orally treated with DHXSD. Besides, glucuronide and sulfate metabolites were also determined in rat plasma after hydrolysis. This is the first method developed for the simultaneous quantification of multiple compounds of DHXSD in vivo. Our study provides relevant information on the pharmacokinetics of DHXSD and the relationship between the compounds of DHXSD and their therapeutic effects. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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