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Cited by 25Traditional Chinese Medicine AnalysisAnalytical Methods in PharmaceuticalsPhytochemistry and Biological Activities

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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

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Choi, Won-Gu, Kim, Ju-Hyun, Kim, Dong Kyun, Lee, Yongnam, Yoo, Ji Seok, Shin, Dae Hee, Lee, Hye Suk·2018·Pharmaceutics
DOI 10.3390/pharmaceutics10030143PMC PMC6161084
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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.

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Figure 1 Metabolic pathways of chlorogenic acid, neochlorogenic acid, and cryptochlorogenic acid in rats and humans.
Figure 1 Metabolic pathways of chlorogenic acid, neochlorogenic acid, and cryptochlorogenic acid in rats and humans.CC BY · PubMed Central
Figure 2 Product ion spectra of (A) chlorogenic acid (CGA), (B) caffeic acid (CA), (C) CA-3-G, (D) ferulic acid (FA), and (E) FA-d3 (IS).
Figure 2 Product ion spectra of (A) chlorogenic acid (CGA), (B) caffeic acid (CA), (C) CA-3-G, (D) ferulic acid (FA), and (E) FA-d3 (IS).CC BY · PubMed Central
Figure 3 Selected reaction monitoring chromatograms of (A) rat blank plasma, (B) rat plasma spiked with CGA (0.5 ng/mL), NCGA (0.5 ng/mL), CCGA (2.5 ng/mL), CA (2.5 ng/mL), CA-3-G (2.5 ng/mL), CA-4-G (2.5 ng/mL), and FA (12.5 ng/mL) at lower limits of quantification (LLOQ) level, and (C) rat plasma obtained 5 min after oral administration of YRA-1909 at a dose of 100 mg/kg to a male SD rat. 1, NCGA; 2, CGA; 3, CCGA; 4, CA; 5, CA-4-G; 6, CA-3-G; 7, FA; 8, FA-d3.
Figure 3 Selected reaction monitoring chromatograms of (A) rat blank plasma, (B) rat plasma spiked with CGA (0.5 ng/mL), NCGA (0.5 ng/mL), CCGA (2.5 ng/mL), CA (2.5 ng/mL), CA-3-G (2.5 ng/mL), CA-4-G (2.5 ng/mL), and FA (12.5 ng/mL) at lower limits of quantification (LLOQ) level, and (C) rat plasma obtained 5 min after oral administration of YRA-1909 at a dose of 100 mg/kg to a male SD rat. 1, NCGA; 2, CGA; 3, CCGA; 4, CA; 5, CA-4-G; 6, CA-3-G; 7, FA; 8, FA-d3.CC BY · PubMed Central
Figure 4 Mean plasma concentration-time profiles of (A) CGA, (B) CCGA, (C) neochlorogenic acid (NCGA), (D) CA, (E) CA-3-G, and (F) CA-4-G after a single oral administration of YRA-1909 at the doses of 25 (◯, n = 6), 50 (△, n = 12), and 100 (☐, n = 6) mg/kg (equivalent to 1.2, 2.4, and 4.8 mg/kg CGA; 0.275, 0.55, and 1.10 mg/kg NCGA; 0.87, 1.74 and 3.48 mg/kg CCGA) and repeated administration of 50 mg/kg YRA-1909 once/day for seven days (▼, n = 6) in male rats. Each point represents mean ± SD.
Figure 4 Mean plasma concentration-time profiles of (A) CGA, (B) CCGA, (C) neochlorogenic acid (NCGA), (D) CA, (E) CA-3-G, and (F) CA-4-G after a single oral administration of YRA-1909 at the doses of 25 (◯, n = 6), 50 (△, n = 12), and 100 (☐, n = 6) mg/kg (equivalent to 1.2, 2.4, and 4.8 mg/kg CGA; 0.275, 0.55, and 1.10 mg/kg NCGA; 0.87, 1.74 and 3.48 mg/kg CCGA) and repeated administration of 50 mg/kg YRA-1909 once/day for seven days (▼, n = 6) in male rats. Each point represents mean ± SD.CC BY · PubMed Central

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Metadata

Authors
Choi, W.-G., Kim, J.-H., Kim, D. K., Lee, Y., Yoo, J. S., Shin, D. H., & Lee, H. S.
Affiliations
  • Catholic University of Korea (KR)
  • Yeungnam University (KR)
  • Central R&D Institute, YUNGJIN PHARM. CO., LTD., Suwon 16229, Korea
Corresponding author
Lee, Hye Suk
ORCID
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2018-09-02
Volume
10
Issue
3
Pages
143
ISSN
1999-4923 (ISSN-L)
DOI
10.3390/pharmaceutics10030143
PMC
PMC6161084
OpenAlex
W2889429701
Cited by
25
References
30
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 3
FWCI
3.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmaceutics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Ministry of Trade, Industry and Energy (Technology Innovation Program (10051145))
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Traditional Chinese Medicine Analysis
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and Biological Activities
Keywords
chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, caffeic acid, ferulic acid, pharmacokinetics, oral administration, rat plasma, rheumatoid arthritis, herbal medicine

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CoChat. (2026). Citation check: 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. https://app.cochat.ai/papers/10.3390/pharmaceutics10030143
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Choi, W.-G., Kim, J.-H., Kim, D. K., Lee, Y., Yoo, J. S., Shin, D. H., & Lee, H. S. (2018). 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. https://doi.org/10.3390/pharmaceutics10030143

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