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Influence of traditional Chinese medicines on the in vivo metabolism of lopinavir/ritonavir based on UHPLC-MS/MS analysis

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Journal of Pharmaceutical Analysis 2022年第2期12卷 270-277页

作者： Linlin Li Xinxiang Yu Dongmin Xie Ningning Peng Weilin Wang Decai Wang Binglong Li Department of Clinical Pharmacy School of PharmacyShandong First Medical University&Shandong Academy of Medical SciencesTai'anShandong271016China

A fast,reliable,and cost-effective liquid chromatography-tandem mass spectrometry method was established to determine the effects of the traditional Chinese medicine employed to treat coronavirus disease 2019,namely,Lianhua Qingwen granules,Huoxiang Zhengqi capsules,Jinhua Qinggan granules,Shufeng Jiedu capsules,and Angong Niuhuang pills,on the pharmacokinetics of lopinavir/ritonavir in *** samples were prepared using the protein precipitation method and atazanavir was selected as the internal standard(IS).Separation was performed on an Agilent ZORBAX eclipse plus C18(2.1 mm×50 mm,1.8 μm)column using acetonitrile and water containing 0.1%formic acid as the mobile phase for gradient *** flow rate was 0.4 mL/min and the injection volume was 2 μ*** Jet Stream electrospray ionization was used for mass spectrometry detection under positive ion multiple reaction monitoring mode at a transition of m/z 629.3→447.3 for lopinavir,m/z 721.3→296.1 for ritonavir,and m/z 705.4→168.1 for the *** method showed good linearity in the concentration range of 25→2500 ng/mL(r=0.9981)for lopinavir and 5e500 ng/mL(r=0.9984)for *** intra-day and inter-day precision and accuracy were both within±15%.Items,such as dilution reliability and residual effect,were also within the acceptable *** method was used to determine the effects of five types of traditional Chinese medicines on the pharmacokinetics of lopinavir/ritonavir in *** pharmacokinetic results showed that the half-life of ritonavir in the groups administered Lianhua Qingwen granules and Huoxiang Zhengqi capsules combined with lopinavir/ritonavir was prolonged by approximately 1.5-to 2-fold relative to that in the control ***,the pharmacokinetic parameters of lopinavir were ***,the results of this study offer important theoretical parameters for the effective clinical use of five types of traditional Chinese medicines combined with lopinavir/ritonavir to reduce the

关键词： Lopinavir/ritonavir Combination of Chinese and western medicine Drug-drug interaction Ultra high-performance liquid chromatography-tandem mass spectrometry Pharmacokinetics COVID-19

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Pharmacokinetics of oxiracetam and its degraded substance (HOPAA) after oral and intravenous administration in rats

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Asian Journal of Pharmaceutical Sciences 2014年第6期9卷 342-347页

作者： Xinhuan Wan Xiaohong Liu Zheng Liu Panqin Ma Feitong Zhang Xiangrong Zhang Jin Sun School of Pharmacy Shenyang Pharmaceutical UniversityShenyangChina Ningxia Kangya Pharmaceutical Co. LtdYinchuangChina School of Traditional Chinese Medicine Shenyang Pharmaceutical UniversityShenyangChina GLP Center School of Life Science and BiopharmacyShenyang Pharmaceutical UniversityShenyangChina

The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS *** groups of rats after an overnight fasted received 10 g/kg(n=6)oxiracetam suspensions orally,and 2 g/kg(n=6)normal or degraded oxiracetam injections intravenously via a caudal tail vein,*** the pharmacokinetic experiment,a simple safety evaluation testwas conducted on the degraded oxiracetam injections containing 16.16% HOPAA in *** was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within twoweeks,demonstrating that HOPAA was non-toxic in *** intravenous administration of the normal injections,the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination *** values of t_(1/2)were 3.1±1.5 h for oxiracetamand 0.8±0.2 h for HOPAA,andthemean residencetimes(MRT)were 1.2±0.1h and 0.8±0.1h,*** and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal *** pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes,and both had a longer t_(1/2) and MRT than those of intravenous *** of HOPAA in three groupswere calculated based on AUC_(0-t) values of the two *** quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetamat the same time for every ***,the values of absolute bioavailability of oxiracetam were about 8.0%and 7.4%calculated by the normal or degraded oxiracetam injections,whichwere far less than the value of 75%reported in literature,indicating the necessity of further study.

关键词： Oxiracetam 4-Hydroxy-2-oxo-1-pyrrolidine acetic acid(HOPAA) High performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) Pharmacokinetics Toxicity

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