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Development of a rapid UPLC-MS/MS method for the determination of toddalolactone in mouse blood and its application in pharmacokinetics

Zhou Jing, Wang Hongzhe, Miao Caiyun, Yao Yunxi, Ma Jianshe

Acta Chromatographica

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2022

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Vol. 34, no. 1

18--23

EN

A rapid and simple UPLC-MS/MS method was developed to determine toddalolactone in mouse blood and applied to measure the pharmacokinetics of toddalolactone in mice. Blood samples were first preprocessed by ethyl acetate liquid-liquid extraction. Oxypeucedanin hydrate (internal standard, IS) and toddalolactone were gradient eluted from a UPLC BEH C18 column using a mobile phase consisting of acetonitrile and water (0.1% formic acid). Using electrospray ionization (ESI) as the ionization source, multiple reaction monitoring was used to detect the precursor and product ions of m/z 309.2 and 205.2, respectively, for toddalolactone and of m/z 305.1 and 203.0 for IS, respectively, for quantitative detection. A calibration curve was run over the concentration range of 5–4,000 ng/mL (r > 0.995). The matrix effects ranged from 93.5 to 98.4%, and the recovery was higher than 77.3%. The precision was less than 13%, and the accuracy ranged from 90.9 to 108.4%. The developed UPLC-MS/MS method was successfully used for measuring the pharmacokinetics of toddalolactone in mice after oral (20 mg/kg) and intravenous administration (5 mg/kg), and the absolute bioavailability of toddalolactone was 22.4%.

2

Determination of narciclasine in mouse blood by UPLC-MS/MS and its application to a pharmacokinetic study

Ren Ke, Feng Tiantian, Shi Hai, Ma Jianshe, Jin Yongxi

Acta Chromatographica

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2022

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Vol. 34, no. 2

115--119

EN

Narciclasine is a 7-hydroxy derivative of lycorisidine. It was the first alkaloid isolated from the stem of narcissus (Amaryllidaceae) in 1967. Six mice were given narciclasine (5 mg/kg) by intravenous administration. A UPLC-MS/MS method was developed to determine narciclasine in mouse blood. Tectorigenin (internal standard, IS) and narciclasine were gradient eluted by mobile phase of methanol and 0.1% formic acid in a BEH C18 column. The multiple reaction monitoring (MRM) of m/z 308.1→248.1 for narciclasine and m/z 301.1→286.0 for IS with an electrospray ionization (ESI) source was used for quantitative determination. The calibration curve ranged from 1 to 6,000 ng/mL. The accuracy was from 92.5 to 107.3%, and the matrix effect was between 103.6 and 107.4%. The developed UPLC-MS/MS method was successfully applicated to a pharmacokinetic study of narciclasine in mice after intravenous administration (5 mg/kg).

3

Pharmacokinetics and bioavailability of liensinine in mouse blood by UPLC-MS/MS

Tong Shuhua, Zeng Yuqi, Ma Jianshe, Wen Congcong

Acta Chromatographica

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2021

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Vol. 33, no. 4

333--337

EN

Liensinine is a bisbenzyltetrahydroisoquinoline alkaloid extracted from lotus (Nelumbo nucifera GAERTNER., Nelumbonaceae), especially in its embryo loti “Lien Tze Hsin” (green embryo of mature seed). A rapid and simple UPLC-MS/MS method was developed to determine liensinine in mouse blood and its application to a pharmacokinetic study. The blood samples were preprocessed by protein precipitation using acetonitrile. Midazolam (internal standard, IS) and liensinine were gradient eluted by mobile phase of methanol and water (0.1% formic acid) in a Waters UPLC BEH C18 column. The multiple reaction monitoring of m/z 611.3 → 206.1 for liensinine and m/z 326.2 → 291.1 for IS with an electrospray ionization (ESI) source was used for quantitative detection. The calibration curve ranged from 0.5 to 400 ng/mL (r > 0.995). The accuracy ranged from 92.2 to 108.2%, the precision of intra-day and inter-day was less than 14%, and the matrix effect was between 100.0% and 109.6%, the recovery was better than 71.0%. The developed UPLC-MS/MS method was successfully used for a pharmacokinetic study of liensinine in mice after oral (5 mg/kg) and intravenous administration (1 mg/kg), and the absolute availability of liensinine was 1.8%.

4

Determination and pharmacokinetics and bioavailability of O-demethyl nuciferine in mice by UPLC–MS/MS

Wu Haiya, Lu Mengrou, He Jiamin, Huang Miaoling, Zheng Aote, Zhang Meiling, Wen Congcong, Ye Jufen

Acta Chromatographica

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2019

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Vol. 31, no. 3

222--227

EN

In this study, a precise, rapid, and accurate ultra-performance liquid chromatography–tandem mass spectrometer (UPLC–MS/MS) method for the quantitation of O-demethyl nuciferine in mouse blood was developed, and pharmacokinetics of O-demethyl nuciferine was studied for the first time after sublingual injection and gavage. The study was performed with an UPLC ethylene bridged hybrid (UPLC BEH) (2.1 mm × 50 mm, 1.7 μm) column at 30 °C, using diazepam as the internal standard (IS). The mobile phase consisted of acetonitrile–10 mmol/L ammonium acetate (containing 0.1% formic acid), with a flow rate of 0.4 mL/min for 4 min run time. Multiple reaction monitoring (MRM) modes of m/z 282.1→219.0 for O-demethyl nuciferine and m/z 296.2→265.1 for IS were utilized to conduct quantitative analysis. Protein in mouse blood was directly precipitated with acetonitrile for sample preparation. The linear range was 1–500 ng/mL with r > 0.995, and the lower limits of quantification (LLOQ) was 1 ng/mL. The intra- and inter-day precision of O-demethyl nuciferine in mouse blood were RSD < 14% and RSD < 15%, respectively.r The accuracy ranged from 89.0% to 110.7%, with a recovery higher than 88.9%, while the matrix effect was between 103.1% and 108.7%. We further applied this UPLC–MS/MS method to the pharmacokinetic study on O-demethyl nuciferine after sublingual injection and gavage and determined the bioavailability to be 6.4%.

5

Induction of Micronuclei in Mice Bone Marrow Cells by Cobalt and Copper Chlorides

Goc Rasgele P., Kekecoglu M., Gokalp Muranli F. D.

Archives of Environmental Protection

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2013

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Vol. 39, no. 1

75-82

EN

The aim of our research was to investigate the genotoxic effects of cobalt chloride and copper chloride in mouse bone marrow cells using the micronucleus (MN) assay. The three different concentrations of cobalt chloride (11.2, 22.5 and 45 mg kg-1) and copper chloride (1.17, 2.35 and 4.70 mg kg-1) were injected intraperitoneally to mice for 24 and 48 hours. It was observed that both of these heavy metals induced a signifi cant increase in frequency of micronucleated polychromatic erythrocytes (MNPCE) at different concentrations in mice for 24 and 48 hours when compared with the control. Furthermore, the signifi cant reduction for the polychromatic erythrocyte/normochromatic erythrocyte (PCE/NCE) ratio which is indicative of bone marrow cytotoxicity was observed in bone marrow cells which were treated with copper chloride at all concentrations for 24 and 48 hours. No reduction of the PCE/NCE ratio was observed both 24 and 48 hours after all the doses of cobalt chloride tested as compared to the negative control. These results lead us to the conclusion that copper chloride may have genotoxic and cytotoxic properties due to induction in the frequency of MN and a reduction in PCE/NCE ratio in bone marrow cells of mice, whereas cobalt chloride induced only genotoxic effect in mice bone marrow.

6

Small mammals in the diet of the Tawny Owl (Strix aluco L.) in Central European Lowland

Żmihorski M., Balciauskiene L., Romanowski J.

Polish Journal of Ecology

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2008

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Vol. 56, nr 4

693-700

EN

We analysed the variation of small mammal species composition in the Tawny Owl Strix aluco L. diet in forest habitats of Central European Lowland. We used published and unpublished materials from forest-dominated landscapes in Lithuania (n = 7 locations), Poland (n = 8) and East Germany (n = 1); marginal localities were ca. 870 km from each other. We recorded that in Central European Lowland the proportion of Arvicolidae in the Tawny Owl diet significantly increased, while that of Muridae decreased toward north-east. The proportion of less common rodent species (including Gliridae and Sicita betulina Pallas) in the diet also increased significantly toward NE. We did not record any trend of small mammals diversity along the analysed transect. We suggest that the change of Arvicolidae to Muridae ratio toward north-east can be caused by the replacement of mice with boreal vole species in small mammal community. Small mammal diversity in Central Europe is subject of discussion.