Metabolic Profile of Isocorynoxeine in Rats Obtained by Ultra-High Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry

• Published in: European journal of drug metabolism and pharmacokinetics Vol. 41; no. 5; pp. 615 - 626
• Main Authors: Zhao, Lizhu, Qi, Wen, Chen, Fangfang, Sun, Jiahong, Yuan, Dan
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.10.2016
• Subjects: Animals; Bile - metabolism; Biomedical and Life Sciences; Biomedicine; Chromatography, High Pressure Liquid - methods; Human Physiology; Indole Alkaloids - metabolism; Male; Medical Biochemistry; Metabolic Networks and Pathways - physiology; Metabolome - physiology; Original Paper; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pharmacy; Rats; Rats, Wistar; Tandem Mass Spectrometry - methods; Urine - chemistry; Accurate Mass; Major Urinary Metabolite; Bile Sample; Molecular Formula; Authentic Standard
• ISSN: 0378-7966; 2107-0180
• DOI: 10.1007/s13318-015-0287-0

Background and Objective Isocorynoxeine (IC), a major alkaloid found in Uncaria rhynchophylla , exhibits wide beneficial effects on the cardiovascular and cardiocerebral vascular systems. Its metabolic pathway, however, has not been well studied yet. In this study, an ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (U-HPLC/Q-TOFMS) method was developed to investigate IC metabolism in plasma, urine and bile in rats given IC orally at 40 mg/kg. Methods Nine male Wistar rats were given IC 40 mg/kg orally. Blood, urine and bile samples were collected at pre-specified times to measure the concentration of IC. Results A total of 35 metabolites were tentatively identified by the co-chromatography of biosamples and comparison of the retention time, characteristic molecular ions and fragment ions with those of the authentic standards or tentatively identified by MS/MS determination along with MassFragment software. Among them, 18, 33 and 18 metabolites were found in plasma, urine and bile samples, respectively. The relative percentage area of each metabolite was also determined to better understand the major metabolic pathways of IC in rats. Conclusions The result indicates that IC undergoes extensive metabolism in vivo, mainly including hydrolysis, oxidation, isomerization, demethylation, epoxidation, reduction, glucuronidation, hydroxylation and N -oxidation, which is helpful for the further pharmacokinetic study of IC in vivo.