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超高效液相色谱-串联四极杆质谱联用同时测定大鼠血浆中的六种活性成分:在叶的药代动力学研究中的应用

Simultaneous UPLC-TQ-MS/MS determination of six active components in rat plasma: application in the pharmacokinetic study of leaves.

作者信息

Ning Zi-Wan, Zhai Li-Xiang, Peng Jiao, Zhao Ling, Huang Tao, Lin Cheng-Yuan, Chen Wei-Hong, Luo Zhen, Xiao Hai-Tao, Bian Zhao-Xiang

机构信息

1Clinical Division, School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road 7, Kowloon, Hong Kong SAR China.

2School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060 China.

出版信息

Chin Med. 2019 Aug 6;14:28. doi: 10.1186/s13020-019-0248-7. eCollection 2019.

DOI:10.1186/s13020-019-0248-7
PMID:31406501
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6685155/
Abstract

BACKGROUND

(Batal.) Ijinskaja (CP) is a monotypic genus plant, also called sweet tea tree that belongs to the Juglandaceae family, which is mainly distributed in the subtropical highlands in China. Our previous work has verified that CP leaves exhibit a potent hyperglycemic effect by inhibiting pancreatic β cell apoptosis through the regulation of MPAK and Akt signaling pathways. However, the components that contribute to this potential health benefit remain undiscovered.

METHOD

A sensitive, reliable, and validated ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-TQ-MS/MS) method was developed to simultaneously determine the presence of six active components (neochlorogenic acid, chlorogenic acid, quercetin-3--glucuronide, kaempferol-3--rhamnoside, quercetin, and kaempferol) in rat plasma after a single oral administration (in a dosage of 10.5 g/kg) of an extract of CP leaves to rats. The separation was performed on a Waters ACQUITY BEH C column (50 mm × 2.1 mm, 1.7 μm). The detection was conducted by multiple reaction monitoring (MRM) in negative ionization mode. The two highest abundant MRM transitions without interference were optimized for each analyte. Acetonitrile and formic acid aqueous solution (0.1%) was used as the mobile phase at a flow rate of 0.3 ml/min.

RESULT

The precision, accuracy, and recovery all satisfied the criteria of international guidance (Bioanalytical Method Validation Guidance for Industry, Food and Drug Administration), and the analytes were stable in plasma for all tested conditions. The main pharmacokinetic parameters were calculated by plasma concentration versus time profiles using the pharmacokinetics program.

CONCLUSION

The pharmacokinetic parameters of each compound can facilitate future clinical studies.

摘要

背景

(巴塔)伊金斯基茶(CP)是一种单型属植物,也被称为甜茶树,属于胡桃科,主要分布在中国亚热带高地。我们之前的研究已经证实,CP叶通过调节MPAK和Akt信号通路抑制胰腺β细胞凋亡,从而具有显著的降血糖作用。然而,促成这种潜在健康益处的成分尚未被发现。

方法

建立了一种灵敏、可靠且经过验证的超高效液相色谱-三重四极杆串联质谱联用(UPLC-TQ-MS/MS)方法,用于在大鼠单次口服(剂量为10.5 g/kg)CP叶提取物后,同时测定大鼠血浆中六种活性成分(新绿原酸、绿原酸、槲皮素-3-O-葡萄糖醛酸、山柰酚-3-O-鼠李糖苷、槲皮素和山柰酚)的含量。分离在Waters ACQUITY BEH C柱(50 mm×2.1 mm,1.7 μm)上进行。检测采用负离子模式下的多反应监测(MRM)。针对每种分析物优化了两个最高丰度且无干扰的MRM转换。乙腈和0.1%甲酸水溶液用作流动相,流速为0.3 ml/min。

结果

精密度、准确度和回收率均符合国际指南(美国食品药品监督管理局工业生物分析方法验证指南)的标准,并且在所有测试条件下分析物在血浆中均稳定。主要药代动力学参数通过使用药代动力学程序根据血浆浓度-时间曲线计算得出。

结论

每种化合物的药代动力学参数有助于未来的临床研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e489/6685155/ca811fc72d71/13020_2019_248_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e489/6685155/8ea7be458ec1/13020_2019_248_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e489/6685155/aa9a3b32f177/13020_2019_248_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e489/6685155/02dc89e8ee49/13020_2019_248_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e489/6685155/ca811fc72d71/13020_2019_248_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e489/6685155/8ea7be458ec1/13020_2019_248_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e489/6685155/aa9a3b32f177/13020_2019_248_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e489/6685155/02dc89e8ee49/13020_2019_248_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e489/6685155/ca811fc72d71/13020_2019_248_Fig4_HTML.jpg

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