2. Academic Validation
  3. Pharmacokinetic and Metabolism Studies of Curculigoside C by UPLC-MS/MS and UPLC-QTOF-MS

Pharmacokinetic and Metabolism Studies of Curculigoside C by UPLC-MS/MS and UPLC-QTOF-MS

  • Molecules. 2018 Dec 21;24(1):21. doi: 10.3390/molecules24010021.
Di Wu 1,  Han Wang 2,  Jing Tan 3,  Cuizhu Wang 4,  Hongqiang Lin 5,  Hailin Zhu 6,  Jinping Liu 7,  Pingya Li 8,  Jianyuan Yin 9
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun 130021, China. dwu15@mails.jlu.edu.cn.
  • 2 School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun 130021, China. hanw17@mails.jlu.edu.cn.
  • 3 School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun 130021, China. tanjing17@mails.jlu.edu.cn.
  • 4 School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun 130021, China. wangcz15@mails.jlu.edu.cn.
  • 5 School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun 130021, China. linhq17@mails.jlu.edu.cn.
  • 6 School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun 130021, China. 13578965875@163.com.
  • 7 School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun 130021, China. liujp@jlu.edu.cn.
  • 8 School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun 130021, China. lipy@jlu.edu.cn.
  • 9 School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun 130021, China. yinjy@jlu.edu.cn.
PMID: 30577595 DOI: 10.3390/molecules24010021
Abstract

Pharmacokinetic and metabolism studies were carried out on curculigoside C (CC), a natural product with good antioxidant and neuroprotective effects, with the purpose of investigating the effects of the hydroxyl group at C-3' in curculigoside. A rapid and sensitive method with UPLC-MS was developed and fully validated for the first time in the pharmacokinetic analysis for quantification of CC in rat plasma. The assay was linear (R² > 0.9984) over the concentration range of 1⁻2500 ng/mL, with the lower limit of quantification (LLOQ) being 1 ng/mL. The intra-day and inter-day precision (expressed as relative standard deviation, RSD) ranged from 4.10% to 5.51% and 5.24% to 6.81%, respectively. The accuracy (relative error, RE) ranged from -3.28% to 0.56% and -5.83% to -1.44%, respectively. The recoveries ranged from 92.14% to 95.22%. This method was then applied to a pharmacokinetic study of rats after intragastric administration of 15, 30 and 60 mg/kg CC. The results revealed that CC exhibited rapid oral absorption (Tmax = 0.106 h, 0.111 h, and 0.111 h, respectively), high elimination (t1/2 = 2.022 h, 2.061 h, and 2.048 h, respectively) and low absolute bioavailability (2.01, 2.13, and 2.39%, respectively). Furthermore, an investigation on the metabolism of CC was performed by UPLC-QTOF-MSE. Twelve metabolites of CC from plasma, bile, urine and faeces of rats were confirmed. The main metabolic pathways of CC, which involve dehydration, glucosylation, desaturation, formylation, cysteine conjugation, demethylation and sulfonation, were profiled. In conclusion, this research has developed a sensitive quantitative method and demonstrated the metabolism of CC in vivo.

Keywords

UPLC-MS; curculigoside C; metabolism; pharmacokinetics.

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