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Pharmaceutics 2018, 10(3), 143; https://doi.org/10.3390/pharmaceutics10030143

Simultaneous Determination of Chlorogenic Acid Isomers and Metabolites in Rat Plasma Using LC-MS/MS and Its Application to A Pharmacokinetic Study Following Oral Administration of Stauntonia Hexaphylla Leaf Extract (YRA-1909) to Rats

1
BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy and Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea
2
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Korea
3
Central R&D Institute, YUNGJIN PHARM. CO., LTD., Suwon 16229, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 9 August 2018 / Revised: 27 August 2018 / Accepted: 28 August 2018 / Published: 2 September 2018
(This article belongs to the Special Issue Drug Metabolism, Pharmacokinetics and Bioanalysis)
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Abstract

Stauntonia hexaphylla leaf extract (YRA-1909), which is widely used for the antirheumatic properties, has been under phase 2 clinical trials in patients with rheumatoid arthritis since April 2017. Liquid chromatography-tandem mass spectrometric method while using liquid–liquid extraction with ethyl acetate was validated for the simultaneous determination of the major active components of YRA-1909, including chlorogenic acid (CGA), neochlorogenic acid (NCGA), cryptochlorogenic acid (CCGA), and their metabolites (i.e., caffeic acid (CA), caffeic acid 3-O-glucuronide (CA-3-G), caffeic acid 4-O-glucuronide (CA-4-G), and ferulic acid (FA)) in rat plasma and applied to a pharmacokinetic study of YRA-1909 in rats. Seven analytes were separated on Halo C18 while using gradient elution of formic acid and methanol, and then quantified in selected reaction monitoring mode whle using negative electrospray ionization. Following oral administration of YRA-1909 at doses of 25, 50, and 100 mg/kg to male Sprague-Dawley rats, CGA, NCGA, and CCGA were rapidly absorbed and metabolized to CA, CA-3-G, and CA-4-G. The area under the plasma concentration-time curve (AUClast) of CGA, NCGA, CCGA, and three metabolites linearly increased as the YRA-1909 dose increased. Other pharmacokinetic parameters were comparable among three doses studied. AUClast values for CA, CA-3-G, and CA-4-G exceeded those for CGA, NCGA, and CCGA. View Full-Text
Keywords: Stauntonia hexaphylla leaf extract; YRA-1909; pharmacokinetics; chlorogenic acid; neochlorogenic acid; cryptochlorogenic acid; caffeic acid; caffeic acid O-glucuronides; LC-MS/MS Stauntonia hexaphylla leaf extract; YRA-1909; pharmacokinetics; chlorogenic acid; neochlorogenic acid; cryptochlorogenic acid; caffeic acid; caffeic acid O-glucuronides; LC-MS/MS
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Choi, W.-G.; Kim, J.-H.; Kim, D.K.; Lee, Y.; Yoo, J.S.; Shin, D.H.; Lee, H.S. Simultaneous Determination of Chlorogenic Acid Isomers and Metabolites in Rat Plasma Using LC-MS/MS and Its Application to A Pharmacokinetic Study Following Oral Administration of Stauntonia Hexaphylla Leaf Extract (YRA-1909) to Rats. Pharmaceutics 2018, 10, 143.

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