LC–MS/MS determination and comparative pharmacokinetics of strychnine, brucine and their metabolites in rat plasma after intragastric administration of each monomer and the total alkaloids from Semen Strychni

Lin, Aijun; Su, Xiaochun; She, Dan; Qiu, Kuncheng; He, Qianmei; Liu, Yiming

doi:10.1016/j.jchromb.2015.11.012

Cited by 34 publications

(27 citation statements)

References 9 publications

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“…Brucine was absorbed quickly and the peak concentration of brucine occurred at around 0.4 h after the oral administration. It was eliminated with an average t 1/2 of 2.6 h in rats, which were in close accordance with the data reported previously . When brucine was co‐administered with single dose of liquorice water extract, the C max , AUC 0‐t , AUC 0‐∞ of brucine were significantly decreased by 30.0%, 22.9%, and 21.8%, respectively.…”

Section: Resultssupporting

confidence: 90%

“…Recently, a rapid, sensitive HPLC with ultrasound‐assisted mixed cloud point extraction method was developed and validated to simultaneously quantify strychnine, brucine, strychnine N ‐oxide and brucine N ‐oxide in rat plasma simultaneously, in which the lower limit of quantification (LLOQ) is 1 ng/mL . An LC–MS/MS method with high sensitivity (0.5 ng/mL for strychnine, brucine, 0.1 ng/mL for strychnine N ‐oxide and brucine N ‐oxide) was also established . On the other hand, systematic quantitative analysis of the active constituents of liquorice has been reported in both in vitro and in vivo samples .…”

Section: Introductionmentioning

confidence: 99%

“…18 An LC-MS/MS method with high sensitivity (0.5 ng/mL for strychnine, brucine, 0.1 ng/mL for strychnine N-oxide and brucine N-oxide) was also established. 19 On the other hand, systematic quantitative analysis of the active constituents of liquorice has been reported in both in vitro 20 and in vivo samples. 15,21 Nevertheless, the sensitivity of liquiritigenin (LLOQ 12.5 ng/mL), isoliquiritigenin (LLOQ 12.5 ng/mL), and liquiritin (LLOQ 7.5 ng/mL) in previously reported methods was not enough to determine the plasma concentration of rats in our research for pharmacokinetic study.…”

Section: Introductionmentioning

confidence: 99%

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An LC–MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study

Zhang

Deng

Wang

et al. 2017

Drug Testing and Analysis

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Semen Strychni is known for its treatment of rheumatic arthritis with a low therapeutic index. Liquorice contributes a lot in herb detoxification according to the traditional Chinese medicine theory. A simple, rapid, and sensitive liquid chromatography-mass spectrometric method (LC-MS) was developed and validated for simultaneous determination of main bioactive ingredients in liquorice and Semen Strychni in rat plasma. Using moclobemide and cyproterone acetate as the internal standards, the analytes were pretreated via protein precipitation with methanol. An Ultimate AQ-C18 column (3.0 μm, 3.0 × 100 mm) was employed for chromatographic separation, combining with gradient elution. The mobile phase consisted of 0.07% formic acid and 0.12% ammonium acetate in aqueous phase (A) and acetonitrile in organic phase (B). The elution program was as follows: 0-0.5 min, 20% B; 0.5-1 min, 20-60% B; 1-7 min, 60-85% B; and 7-7.5 min, returned to 20% B, then continued to 12 min. Selected reaction monitoring was performed in both positive and negative ESI. Positive mode was adopted for detection of strychnine, brucine, and moclobemide, while negative mode was used for glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, liquiritin, and cyproterone acetate. The method was validated for specificity, linearity, matrix effect, recovery, precision, accuracy, and stability. The results show that this method is sensitive, accurate and robust for biological matrix analysis. Moreover, the proposed method was applied to a pharmacokinetic study in Sprague-Dawley rats for investigating the mechanism of which liquorice detoxifies Semen Strychni.

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Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An LC–MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study

Zhang

Deng

Wang

et al. 2017

Drug Testing and Analysis

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“…Heart, liver, spleen, lung, kidney, and brain tissue were collected and homogenized. Tissue homogenate and plasma were added with 0, 0.2, 0.4, 0.8, 1, 2, 4, 6,8,10,15,20,25,30,35,40,45,50,60,80 and 100 µL of FITC solutions respectively to obtain FITC-tissue homogenate mixture. The fluorescence intensity was measured at 490 nm and 520 nm using a microplate reader.…”

Section: Tissue Distribution Of Fucoidan In Micementioning

confidence: 99%

Study on Absorption Mechanism and Tissue Distribution of Fucoidan

Bai

Zhang

et al. 2020

Molecules

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Fucoidan exhibits several pharmacological activities and is characterized by high safety and the absence of toxic side effects. However, the absorption of fucoidan is not well-characterized. In the present study, fucoidan were labeled with fluorescein isothiocyanate (FITC) and their ability to traverse a monolayer of Caco-2 cells was examined. The apparent permeability coefficients (Papp × 10−6) of FITC-labeled fucoidan (FITC-fucoidan) were 26.23, 20.15, 17.93, 16.11 cm/sec, respectively, at the concentration of 10 μg/mL at 0.5, 1, 1.5 and 2 h. The absorption of FITC-fucoidan was suppressed by inhibitors of clathrin-mediated endocytosis, chlorpromazine, NH4Cl, and Dynasore; the inhibition rates were 84.24%, 74.61%, and 63.94%, respectively. This finding suggested that clathrin-mediated endocytosis was involved in fucoidan transport. Finally, tissue distribution of FITC-fucoidan was studied in vivo after injection of 50 mg/kg body weight into the tail vein of mice. The results showed that FITC-fucoidan targeted kidney and liver, reaching concentrations of 1092.31 and 284.27 μg/g respectively after 0.5 h. In summary, the present work identified the mechanism of absorption of fucoidan and documented its tissue distribution, providing a theoretical basis for the future development of fucoidan applications.

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“…Several analytical methods for the detection of strychnine and brucine in biological samples have been reported. These have included assays based on high‐performance liquid chromatography (HPLC) using UV detection (Chen et al, ), with liquid chromatography–tandem mass spectrometry (LC–MS/MS; Chen, Lai, & Cai, ; Gu et al, ; Gu et al, ; Lin et al, ; Liu, Zhu, Li, Yan, & Lei, ; Xu, Si, & Liu, ). However, none of the current methods are suitable for the determination of the lowest concentrations of strychnine and brucine in our toxicokinetic study.…”

Section: Introductionmentioning

confidence: 99%

Toxicokinetics of strychnine and brucine after the oral administration of Biqi capsule to rats by RRLC–MS/MS

Zheng

Wang

Liu

et al. 2017

Biomedical Chromatography

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Biqi capsule is a well-known traditional Chinese medicine formula that has been widely applied for the clinical treatment of such diseases as rheumatoid arthritis, scapulohumeral periarthritis and cervical spondylopathy. However, there is concern regarding the toxicity of Biqi capsule owing to its active ingredients, strychnine and brucine. To investigate the toxicokinetics of strychnine and brucine after oral administration of Biqi capsule to rats, a sensitive and simple rapid-resolution liquid chromatography/tandem mass spectrometry method was developed to determine the levels of strychnine and brucine in rat plasma. Chromatographic separation was performed on a Capcell Pak C MG II (3.0 μm, 2.0 × 35 mm) column by gradient elution with acetonitrile and 0.2% formic acid as the mobile phase. The method was validated over the range of 0.25-250 ng/mL for strychnine and 0.025-25 ng/mL for brucine. The intra- and inter-day accuracies of strychnine and brucine in rat plasma were 100.3-106.6 and 90.75-106.1% respectively, and the precisions were within 14.2%. The established method was successfully applied to the toxicokinetic study of strychnine and brucine after single and multiple oral administration of Biqi capsule to male and female rats at 0.4, 0.8 and 1.6 g/kg doses. The results showed different toxicokinetic characteristics in the different groups.

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LC–MS/MS determination and comparative pharmacokinetics of strychnine, brucine and their metabolites in rat plasma after intragastric administration of each monomer and the total alkaloids from Semen Strychni

Cited by 34 publications

References 9 publications

An LC–MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study

An LC–MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study

Study on Absorption Mechanism and Tissue Distribution of Fucoidan

Toxicokinetics of strychnine and brucine after the oral administration of Biqi capsule to rats by RRLC–MS/MS

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