A Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain
Chlorogenic acid (5-CQA) is a phenolic natural product that has been reported to improve neurobehavioral disorders and brain injury. However, its pharmacokinetics and distribution in the rat brain remain unclear. In this study, we established a rapid and sensitive UHPLC–MS/MS method for the determin...
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MDPI AG
2023-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/2/178 |
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| author | Chongfei Bai Xiaogang Zhou Lu Yu Anguo Wu Le Yang Jianping Chen Xue Tang Wenjun Zou Jianming Wu Linjie Zhu |
| author_facet | Chongfei Bai Xiaogang Zhou Lu Yu Anguo Wu Le Yang Jianping Chen Xue Tang Wenjun Zou Jianming Wu Linjie Zhu |
| author_sort | Chongfei Bai |
| collection | DOAJ |
| description | Chlorogenic acid (5-CQA) is a phenolic natural product that has been reported to improve neurobehavioral disorders and brain injury. However, its pharmacokinetics and distribution in the rat brain remain unclear. In this study, we established a rapid and sensitive UHPLC–MS/MS method for the determination of 5-CQA in rat plasma, cerebrospinal fluid (CSF), and brain tissue to investigate whether it could pass through the blood–brain barrier (BBB) and its distribution in the rat brain, and a <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) strain paralysis assay was used to investigate the neuroprotective effect of 5-CQA in different brain tissues. Chromatographic separation of 5-CQA and glycyrrhetinic acid (GA, used as internal standard) was completed in 0.5 min, and the full run time was maintained at 4.0 min. Methodological validation results presented a high accuracy (95.69–106.81%) and precision (RSD ≤ 8%), with a lower limit of quantification of 1.0 ng/mL. Pharmacokinetic results revealed that 5-CQA can pass through the BBB into the CSF, but the permeability of BBB to 5-CQA (ratio of mean AUC<sub>0-∞</sub> of CSF to plasma) was only approximately 0.29%. In addition, 5-CQA can penetrate into the rat brain extensively and is distributed with different intensities in different nuclei. A <i>C. elegans</i> strain paralysis assay indicated that the neuroprotective effect of 5-CQA is positively correlated with its content in different brain tissues. In conclusion, our study for the first time explored the BBB pass rate and brain tissue distribution of 5-CQA administered via the tail vein by the UHPLC–MS/MS method and investigated the potential main target area of 5-CQA for neuroprotection, which could provide a certain basis for the treatment of nervous system-related diseases of 5-CQA. |
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| language | English |
| last_indexed | 2024-03-11T08:18:25Z |
| publishDate | 2023-01-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-e6249895dfb14d6293f982fb7ce090622023-11-16T22:36:07ZengMDPI AGPharmaceuticals1424-82472023-01-0116217810.3390/ph16020178A Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat BrainChongfei Bai0Xiaogang Zhou1Lu Yu2Anguo Wu3Le Yang4Jianping Chen5Xue Tang6Wenjun Zou7Jianming Wu8Linjie Zhu9Department of Chinese Materia Medica, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaSchool of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, ChinaDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaChengdu Analytical Applications Center, Shimadzu (China) Co., Ltd., Chengdu 610023, ChinaSchool of Chinese Medicine, The University of Hong Kong, Hong Kong, ChinaChengdu Analytical Applications Center, Shimadzu (China) Co., Ltd., Chengdu 610023, ChinaDepartment of Chinese Materia Medica, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, ChinaDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaChlorogenic acid (5-CQA) is a phenolic natural product that has been reported to improve neurobehavioral disorders and brain injury. However, its pharmacokinetics and distribution in the rat brain remain unclear. In this study, we established a rapid and sensitive UHPLC–MS/MS method for the determination of 5-CQA in rat plasma, cerebrospinal fluid (CSF), and brain tissue to investigate whether it could pass through the blood–brain barrier (BBB) and its distribution in the rat brain, and a <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) strain paralysis assay was used to investigate the neuroprotective effect of 5-CQA in different brain tissues. Chromatographic separation of 5-CQA and glycyrrhetinic acid (GA, used as internal standard) was completed in 0.5 min, and the full run time was maintained at 4.0 min. Methodological validation results presented a high accuracy (95.69–106.81%) and precision (RSD ≤ 8%), with a lower limit of quantification of 1.0 ng/mL. Pharmacokinetic results revealed that 5-CQA can pass through the BBB into the CSF, but the permeability of BBB to 5-CQA (ratio of mean AUC<sub>0-∞</sub> of CSF to plasma) was only approximately 0.29%. In addition, 5-CQA can penetrate into the rat brain extensively and is distributed with different intensities in different nuclei. A <i>C. elegans</i> strain paralysis assay indicated that the neuroprotective effect of 5-CQA is positively correlated with its content in different brain tissues. In conclusion, our study for the first time explored the BBB pass rate and brain tissue distribution of 5-CQA administered via the tail vein by the UHPLC–MS/MS method and investigated the potential main target area of 5-CQA for neuroprotection, which could provide a certain basis for the treatment of nervous system-related diseases of 5-CQA.https://www.mdpi.com/1424-8247/16/2/178chlorogenic acidpharmacokineticsUHPLC–MS/MSdistributionneuroprotection |
| spellingShingle | Chongfei Bai Xiaogang Zhou Lu Yu Anguo Wu Le Yang Jianping Chen Xue Tang Wenjun Zou Jianming Wu Linjie Zhu A Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain Pharmaceuticals chlorogenic acid pharmacokinetics UHPLC–MS/MS distribution neuroprotection |
| title | A Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain |
| title_full | A Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain |
| title_fullStr | A Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain |
| title_full_unstemmed | A Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain |
| title_short | A Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain |
| title_sort | rapid and sensitive uhplc ms ms method for determination of chlorogenic acid and its application to distribution and neuroprotection in rat brain |
| topic | chlorogenic acid pharmacokinetics UHPLC–MS/MS distribution neuroprotection |
| url | https://www.mdpi.com/1424-8247/16/2/178 |
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