Lihua Zuo1, Jia Li1, Lianping Xue1, Qingquan Jia1, Zhuolun Li1, Mengya Zhang1, Mengfan Zhao1, Mengli Wang1, Jian Kang1, Shuzhang Du1, Zhi Sun1.
Abstract
BACKGROUND: Alpiniae oxyphyllae Fructus (AOF), as a traditional Chinese medicine (TCM), is widely used in the treatment of urinary, gastrointestinal and neurologic diseases in China. Although terpenoids are the main active ingredients of AOF, there are few researches on their pharmacokinetics and metabolism.
METHODS: In this study, a sensitive, rapid, accurate and novel ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to evaluate the pharmacokinetic behavior of five terpenoids (oxyphyllenodiol B, (4S*,5E,10R*)-7-oxo-tri-nor-eudesm-5-en-4β-ol, 7-epi-teucrenone, (+)-(4R,5S,7R)-13- hydroxynootkatone, (E)-labda-12,14-dien-15(16)-olide-17-oic acid) in rats after oral administration of AOF extracts. And 27 metabolic metabolites of the five terpenoids were identified by ultra high performance liquid chromatography -Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) based on precise mass and fragment ions.
RESULTS: The established pharmacokinetic analysis method showed good linearity over a wide concentration range, and the lower quantitative limit (LLOQ) were ranged from 0.97 to 4.25 ng/mL. And other validation parameters were within the acceptable range. In addition, 27 metabolites were identified in plasma, urine and feces samples, and the metabolic pathways of five terpenoids were mainly focus on glucoside conjugation, dehydration, desaturation and glycine conjugation.
CONCLUSION: This is the first study on the pharmacokinetics and metabolism of five terpenoids in AOF at the same time, illuminating the disposal process of terpenoids in vivo. It was expected that the results of this study would provide some references for the apprehension of the action mechanism and the further pharmacological study of five terpenoids in AOF. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
BACKGROUND: Alpiniae oxyphyllae Fructus (AOF), as a traditional Chinese medicine (TCM), is widely used in the treatment of urinary, gastrointestinal and neurologic diseases in China. Although terpenoids are the main active ingredients of AOF, there are few researches on their pharmacokinetics and metabolism.
METHODS: In this study, a sensitive, rapid, accurate and novel ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to evaluate the pharmacokinetic behavior of five terpenoids (oxyphyllenodiol B, (4S*,5E,10R*)-7-oxo-tri-nor-eudesm-5-en-4β-ol, 7-epi-teucrenone, (+)-(4R,5S,7R)-13- hydroxynootkatone, (E)-labda-12,14-dien-15(16)-olide-17-oic acid) in rats after oral administration of AOF extracts. And 27 metabolic metabolites of the five terpenoids were identified by ultra high performance liquid chromatography -Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) based on precise mass and fragment ions.
RESULTS: The established pharmacokinetic analysis method showed good linearity over a wide concentration range, and the lower quantitative limit (LLOQ) were ranged from 0.97 to 4.25 ng/mL. And other validation parameters were within the acceptable range. In addition, 27 metabolites were identified in plasma, urine and feces samples, and the metabolic pathways of five terpenoids were mainly focus on glucoside conjugation, dehydration, desaturation and glycine conjugation.
CONCLUSION: This is the first study on the pharmacokinetics and metabolism of five terpenoids in AOF at the same time, illuminating the disposal process of terpenoids in vivo. It was expected that the results of this study would provide some references for the apprehension of the action mechanism and the further pharmacological study of five terpenoids in AOF. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities:
Keywords:
Alpiniae oxyphyllae Fructus; UHPLC-Qorbitrap HRMS; UPLC-MS/MS; metabolite profiling; pharmacokinetics; terpenoids
Year: 2020
PMID： 33334283 DOI： 10.2174/1389200221666201217154219
Source DB: PubMed Journal: Curr Drug Metab ISSN： 1389-2002 Impact factor: 3.731