Identification of metabolites of Si-Ni-San, a traditional Chinese medicine formula, in rat plasma and urine using liquid chromatography/diode array detection/triple-quadrupole spectrometry.
Si-Ni-San (SNS) is a widely used traditional Chinese medicine formula (TCMF) in treating various diseases. However, the in vivo integrated metabolism of its multiple components remains unknown. In this paper, a liquid chromatography coupled with diode array detection and triple-quadrupole spectrometry (LC-DAD-MS/MS) method was developed for detection and identification of SNS metabolites in rat plasma and urine at a normal clinical dosage. Accurate structural elucidation was performed using MS/MS, UV data and n-octanol/water partition coefficient. Based on the proposed strategy, 36 absorbed compounds and 29 metabolites in plasma and 33 metabolites in urine were detected by a highly sensitive MRM method. Our results indicated that phase II reactions (e.g., methylation, glucuronidation and sulfation) were the main metabolic pathways of gallic acid and flavanones, while phase I reactions (e.g., hydroxylation) were the major metabolic reaction for triterpenoid saponins. The metabolite profile analysis of SNS provided a comprehensive understanding of the in vivo metabolic fates of constituents in SNS. Moreover, the results in this work demonstrated the present strategy based on the combination of chromatographic, spectrophotometric, mass-spectrometric, and software prediction to detect and identify metabolites was effective and reliable. And such a strategy may also be extended to investigate the metabolism of other TCMF.
Laboratory of Pharmaceutics, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210046, People's Republic of China.
Zhixiang
Z
Yan
Ying
Y
Chen
Tianxue
T
Li
Jie
J
Zhang
Xinghao
X
Yang
D020003:1-Octanol; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000378:metabolism*; D005419:Flavonoids / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005707:Gallic Acid / Q000097:blood / Q000378:metabolism* / Q000652:urine; D019695:Glycyrrhizic Acid / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D059629:Signal-To-Noise Ratio; D053719:Tandem Mass Spectrometry / Q000379:methods*
D004365:Drugs, Chinese Herbal; D005419:Flavonoids; C510945:shigyaku-san; D005707:Gallic Acid; D019695:Glycyrrhizic Acid; D020003:1-Octanol