Pharmacokinetics of aconitine as the targeted marker of Fuzi (Aconitum carmichaeli) following single and multiple oral administrations of Fuzi extracts in rat by UPLC/MS/MS

Tang, Lan; Gong, Yong; Lv, Chang; Ye, Ling; Liu, Liang; Liu, Zhongqiu

doi:10.1016/j.jep.2011.08.070

Cited by 72 publications

(54 citation statements)

References 12 publications

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“…Some researchers have reported that Aconitum alkaloids were absorbed very quickly while the bioavailability was very low. [12,[18][19][20] Although many pharmacological studies on Aconitum alkaloids have been reported, [21][22][23][24][25] there are few systematic studies available on the pharmacokinetic characteristics and disposal process of the three forms of Aconitum alkaloids. The aim of this study was to determine the biological activities of three forms of Aconitum alkaloids in rat plasma, urine, faeces, and different tissues after oral administration by liquid chromatographytandem mass spectrometry (LC-MS/MS), investigate their disposal process in vivo, and clarify their pharmacokinetic parameters, absorption and metabolic stability by using a Caco-2 cell monolayer model and rat liver microsome incubation system in vitro, hoping that this study would provide references for rational clinical use of the Aconitum tuber, and for further research on the pharmacology or toxicology of this medicinal plant.…”

Section: Introductionmentioning

confidence: 99%

Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats

Hai

Sun

Zhang

et al. 2015

Drug Testing and Analysis

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Aconitine (AC), benzoylaconine (BAC), and aconine (ACN) are three representative alkaloids in Aconitum tubers. Knowing that the drug disposal process in vivo is closely related to the toxicity and efficacy of a drug, it is important to classify the disposal properties of these alkaloids. In this study, the pharmacokinetics of the three alkaloids was investigated. The results showed that the three alkaloids could be quickly absorbed, especially BAC, whose Tmax was 0.31 ± 0.17 h. Their Cmax was 10.99, 3.99, and 4.29 ng·mL(-1) respectively, indicating that AC had better absorption than BAC and ACN. Subsequently, we further investigated their absorption mechanism using the Caco-2 cell monolayer model in vitro. The results showed that they were poorly absorbed, and the absorption of AC and BAC was inhibited by P-gp, while the absorption of ACN was in a form of passive diffusion. The t1/2 of AC, BAC and ACN was 1.41, 9.49, and 3.32 h, respectively, indicating that the metabolic or excretion rate of AC was quicker than that of BAC and ACN. Therefore, their metabolic stability was further investigated by using rat liver microsomes in vitro, which showed that AC was easier to be metabolized than BAC and ACN. The excretion experiments showed that AC and ACN were primarily excreted in urine, while BAC was excreted in faeces. In addition, the results of tissue distribution experiments showed that the three alkaloids distributed throughout all the organs, although the distribution rate of AC was slower than that of BAC and ACN. Copyright © 2015 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%

Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats

Hai

Sun

Zhang

et al. 2015

Drug Testing and Analysis

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“…Pharmacologically active components of Fuzi are diterpenoid alkaloids, including hetisine, fuziline, benzoylmesaconine, aconitine, hypaconitine and mesaconitine (Wang and Zhu, 2010). Some research has been carried out on aconitine, hypaconitine and mesoconitine using various analytical methods, including highperformance liquid chromatography (HPLC; Xiang et al, 2006), liquid chromatography-mass spectrometry (LC-MS; Zhang et al, 2009), LC-MS/MS (Yue et al, 2009) and Ultra high performance liquid chromatography (HPLC)-quadrupole time-of-flight tandem mass spectrometry (TOF/MS) (Tang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a UHPLC‐qTOF‐MS method for quantification of fuziline in rat plasma and its application in a pharmacokinetic study

Gong

et al. 2014

Biomedical Chromatography

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A specific and sensitive UHPLC-qTOF-MS method was developed and validated for quantification of fuziline in rat plasma after oral administration of three dosages. The analyte was separated on an Acquity UPLC BEH C18 column with a total running time of 3 min using a mobile phase of 0.1% formic acid aqueous solution and methanol (80:20, v/v) at a flow-rate of 0.25 mL/min. The calibration curves for fuziline showed good linearity in the concentrations ranging from 1 to 200 ng/mL with correlation coefficients >0.997. The precision, accuracy, recovery and stability were deemed acceptable. The method was applied to a pharmacokinetics study of fuziline in rats. The mean half-life was 5.93, 6.13 and 5.12 h for 1, 2 and 4 mg/kg oral administration of fuziline, respectively. The peak concentration and area under the concentration-time curve increased linearly with the doses. The sum of these results indicated that, in the range of the doses examined, the pharmacokinetics of fuziline in rat was based on first-order kinetics.

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“…It has been used to warm meridians to dissipate cold and treat rheumatic diseases for over two thousand years, and it is called the first medicine for restoring Yang to rescue collapse [1][2][3]. According to the different ways of processing, it is com-monly converted into Fuzi preparations, including Heishunpian (HSP), Baifupian (BFP), Yanfuzi (YFZ), which are recorded in Chinese Pharmacopoeia (2010 editions) [4].…”

Section: Introductionmentioning

confidence: 99%

Multi-composition analysis inRadix Aconiti Lateralisby single marker quantitation

Yang

Yin

Wang

et al. 2014

Acta Chromatographica

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Summary. Traditional Chinese medicine (TCM) has been widely used in many countries for thousands of years and played an indispensable role in the prevention and treatment of diseases, especially the complicated and chronic ones. However, the application of TCM in diseases is still not fully recognized by people around the world, the main reason is that Chinese herb is a very complex mixture containing hundreds of different components. Thus, it is essential to make quality control and evaluation of TCM. A new quality evaluation method, quantitative analysis of multi-components by single marker (QAMS), was developed to the quality control of alkaloids in TCM, a case study on Radix aconiti lateralis, named Fuzi in Chinese. Six alkaloids, including aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylmesaconine, and benzoylhypaconine, were selected as main components to evaluate the quality of Radix aconiti lateralis. The feasibility and accuracy of QAMS were checked by the external standard method, and various high-performance liquid chromatographic instruments and chromatographic conditions were investigated to verify its applicability. Using aconitine as the internal reference substance and the content of aconitine was calculated according to relative correction factors by high-performance liquid chromatography. The present results showed that there was no significant difference observed between the QAMS method and the external standard method with the relative average deviations less than 3.0%, and QAMS is an effective way to control the quality of herbal medicines and seems to be a convenient and accurate approach to analyze multi-composition when reference substances are unavailable.

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Pharmacokinetics of aconitine as the targeted marker of Fuzi (Aconitum carmichaeli) following single and multiple oral administrations of Fuzi extracts in rat by UPLC/MS/MS

Cited by 72 publications

References 12 publications

Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats

Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats

Development and validation of a UHPLC‐qTOF‐MS method for quantification of fuziline in rat plasma and its application in a pharmacokinetic study

Multi-composition analysis inRadix Aconiti Lateralisby single marker quantitation

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