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

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 1; p. 21
• Main Authors: Wu, Di, Wang, Han, Tan, Jing, Wang, Cuizhu, Lin, Hongqiang, Zhu, Hailin, Liu, Jinping, Li, Pingya, Yin, Jianyuan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-12-2018; MDPI
• Subjects: Antioxidants; Benzoates - metabolism; Benzoates - pharmacokinetics; Bioavailability; Chromatography, High Pressure Liquid - methods; Conjugation; curculigoside C; Dehydration; Demethylation; Desaturation; Drug Stability; Glucosides - metabolism; Glucosides - pharmacokinetics; Hydroxyl groups; In vivo methods and tests; Mass spectrometry; Metabolic pathways; Metabolism; Metabolites; Molecular Structure; Natural products; Neuroprotection; Oral administration; Pharmacokinetics; Pharmacology; Plasma; Proteins; Retention; Scientific imaging; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Sulfonation; Tandem Mass Spectrometry - methods; UPLC-MS; pharmacokinetics; UPLC-MS; metabolism; curculigoside C
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24010021

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 (
= 0.106 h, 0.111 h, and 0.111 h, respectively), high elimination (
= 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-MS
. 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.