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Pharmacokinetics of ligustroflavone in rats and tissue distribution in mice by UPLC–MS/MS

Zhou Quan, Zhang Zhiguang, Geng Peiwu, Huang Bingge, Wang Xianqin, Yu Xiaomin

Acta Chromatographica

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2020

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Vol. 32, no. 2

102--106

EN

An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for quantification of ligustroflavone, which was then applied in pharmacokinetics study in rat and tissue distribution in mouse. Twelve male Sprague Dawley rats were used for pharmacokinetics after intravenous (2 or 8 mg/kg) administration of ligustroflavone, six rats for each dose. Twenty-five mice were randomly divided into 5 groups (5 mice for each group, 1 group for each time point) and received 16 mg/kg ligustroflavone via intraperitoneal administration. The linear range of the calibration curve was over 2–2000 ng/mL for ligustroflavone in rat plasma and mouse tissues. The intra-day and inter-day precision expressed in % RSD were less than 14%, and the accuracy was between 88.5% and 108.4%.

2

Study on pharmacokinetics, tissue distribution, and excretion of phloretin and its prodrug 2′,4′,6′,4-Tetra-O-acetylphloretin in rats using LC–MS/MS

Wang Libin, Li Xi, Mi Le, Shen Xin, Feng Tian, Liu Xueying, Wang Qingwei

Acta Chromatographica

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2019

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Vol. 31, no. 1

63--70

EN

2′,4′,6′,4-Tetra-O-acetylphloretin (TAPHL) is a prodrug of phloretin (PHL) in which the OH groups are protected by acetylation. A validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the determination of PHL in rat biological matrices was developed and applied to investigate and compare the pharmacokinetics, tissue distribution, and excretion of PHL and TAPHL in rats following a single oral administration. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification (LLOQ), recovery, and matrix effect. All validation parameters met the acceptance criteria according to regulatory guidelines. The mean pharmacokinetic parameters of tmax, Cmax, AUC(0 − t), CL/F, and t1/2 were observed after oral administration in rats. The data showed that PHL was absorbed and eliminated rapidly from plasma after oral administration. The pharmacokinetic properties are improved, such as the tmax has been prolonged and the area under the curve (AUC) has been enhanced after oral administration of TAPHL to rats. Tissue distribution results indicated that PHL could be rapidly and widely distributed into tissues but could not effectively cross the blood–brain barrier in rats. After oral administration of TAPHL to rats, its tissue distribution to rats was similar as that after oral administration of equimolar PHL. In addition, higher recoveries of PHL following administration of TAPHL indicated that TAPHL might reduce the excretion of PHL from the body by reducing the first pass effect.

3

Simultaneous quantification of five lignans from Schisandra chinensis in various tissues of rats

Su Lian-Lin, Cheng Xue, Ding Xi-Yan, Mao Chun-Qin, Lu Tu-Lin, Hao Min, Li B.-W., Qin Sirui

Acta Chromatographica

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2019

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Vol. 31, no. 2

113--119

EN

In this research study, a rapid, sensitive, and specific high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC–ESI–MS/MS) method was established and validated, in regard to the simultaneous quantification of five sedative and hypnotic lignans (schisandrin, schisandrol B, schisantherin A, deoxyschisandrin, and schisandrin B) in various tissues of rats (including heart, liver, spleen, lung, and kidney). The purpose of the study was to clarify the tissue distribution of the total lignans extract of Schisandra chinensis (SC). Then, the analytes were separated on a MERCK Purospher STAR LP C18 column (250 mm × 4.6 mm, 5 μm), with a mobile phase consisting of 0.05% (v/v) formic acid acetonitrile, and 0.05% (v/v) formic acid water, and a flow rate of 1 mL/min. All of the calibration curves of the five components showed good linearity (r > 0.9950), with ranges of 4.8 to 1920 ng/mL for analytes. The intra-day and inter-day precisions (relative standard deviation [RSD] %) were within 13.76% for all of the analytes. The average recoveries of the five analytes were greater than 85.23%, and the mean value of the matrix effect ranged from 82.3% to 93.4%. The five analytes were confirmed to be stable during the storage, preparation, and analytic procedures. The major target tissues of the total lignans extract of the SC in the rats were the livers and kidneys.

4

Pharmacokinetics of panasenoside in rats and tissue distribution in mice by ultra-performance liquid chromatography tandem mass spectrometry

Chen Ruijie, Lu Mengrou, Tu Xiaoting, Sun Wei, Ye Weijian, Ma Jianshe, Wen Congcong, Wang Xianqin, Geng Peiwu

Acta Chromatographica

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2019

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Vol. 31, no. 2

146--150

EN

We developed an ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method for quantification of panasenoside pharmacokinetics in rat plasma and tissue distribution in mouse. Twelve male Sprague-Dawley rats were used for pharmacokinetics after intravenous (2 or 10 mg/kg) administration of panasenoside, six rats for each dose. Thirty mice were randomly divided into six groups (five mice for each group, one group for each time point) and received 20 mg/kg of panasenoside by intraperitoneal administration. Calibration plots were in the range of 2–2000 ng/mL for panasenoside in rat plasma and 2–3000 ng/mL in mouse tissues. The relative standard deviation (RSD) of inter-day and intra-day precision was less than 14%. The accuracy was between 89.6% and 110.0%. The AUC(0-t) was 160.8 ± 13.0 and 404.9 ± 78.0 ng/mL*h, and t1/2 of 3.2 ± 1.2 and 4.6 ± 1.7 h, CL (clearance) of 10.0 ± 2.0, and 21.4 ± 2.0 L/h/kg after intravenous administration 2 mg/kg and 10 mg/kg of panasenoside, respectively. The tissue distribution results indicated that the panasenoside diffuses rapidly and widely into major organs. The level of panasenoside was highest in mouse liver, followed by kidney, lung, and spleen. The overwhelming accumulation in liver indicated that liver was responsible for the extensive metabolism.

5

Polybrominated diphenyl ethers (PBDEs) in sediment and fish tissues from Lake Chaohu, central eastern China

Yang S., Fu Q., Teng M., Yang J.

Archives of Environmental Protection

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2015

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Vol. 41, no. 2

12--20

EN

Polybrominated diphenyl ethers (PBDEs) levels in environmental media have increased over the last 20-25 years in the world. In aquatic environments PBDEs were found to be accumulated along food chain and Endocrine disruptors toxicity. In this study PBDEs were investigated in sediment and fish tissues from Lake Chaohu in central eastern China. There were 10 PBDEs congeners detected out of all 41 PBDEs. BDE-47 was of the highest with 5.17 ng/g in sediment and 58.47 ng/g in fish. PBDEs were evenly distributed across the surface sediment in the whole lake. It implied that the main source of PBDEs may not be an inflow river like Nanfei. Tissue distribution patterns of PBDEs in four fish species were in the order of BDE-47 > BDE-99 > BDE-100 > BDE-66 > BDE-138 > BDE-183 > BDE-154 > BDE-153. Octa- and deca-BDEs were below the detection limit. The concentrations of all PBDE congeners were higher in gills, livers, and kidneys than those in muscles and adipose tissue. Furthermore, PBDEs in different tissues had some different distribution patterns with fish size. Those discrepancies appeared to be correlated with the PBDEs pollution fluxes varying with the change of the year and their metabolism divergences in fish tissues.