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Simultaneous Determination of Decursin, Decursinol Angelate, Nodakenin, and Decursinol of Angelica gigas Nakai in Human Plasma by UHPLC-MS/MS: Application to Pharmacokinetic Study

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Simultaneous Determination of Decursin, Decursinol Angelate, Nodakenin, and Decursinol of Angelica gigas Nakai in Human Plasma by UHPLC-MS/MS: Application to Pharmacokinetic Study

Sook-Jin Kim et al. Molecules.

Abstract

Coumarins in Cham-dang-gwi, the dried root of Angelica gigas Nakai (AGN), possess pharmacological effects on anemia, pain, infection, and articular rheumatism. The AGN root containes decursin (D), decursinol angelate (DA), nodakenin, and decursinol (DOH), a major metabolite of D and DA. The aim of this study was to develop a simultaneous determination method for these four coumarins in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Chromatographic separation was performed on dual columns (Kinetex® C18 column and Capcell core C18 column) with mobile phase consisting of water and acetonitrile at a flow rate of 0.3 mL/min using gradient elution. Multiple reaction monitoring was operated in positive ion mode with precursors to product ion transition values of m/z 328.9→228.8, 328.9→228.9, 409.4→248.8, and 246.8→212.9 to measure D, DA, nodakenin, and DOH, respectively. Linear calibration curves were fitted over concentration range of 0.05⁻50 ng/mL for these four components, with correlation coefficient greater than 0.995. Inter- and intra-day accuracies were between 90.60% and 108.24%. These precisions were within 11.19% for all components. The established method was then applied to a pharmacokinetic study for the four coumarins after usual dosing in Korean subjects.

Keywords: UHPLC-MS/MS; decursin; decursinol; decursinol angelate; nodakenin.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of the four coumarins and papaverine as an IS. (A) decursin, (B) decursinol angelate, (C) nodakenin, (D) decursinol, and (E) papaverine (IS).
Figure 2
Figure 2
Full scan product ions of precursor ions of (A) decursin (328.8→228.8), (B) decursinol angelate (328.9→228.9), (C) nodakenin (409.4→248.8), and (D) decursinol (246.8→212.9).
Figure 3
Figure 3
Representative MRM chromatograms of AGN root extract in human plasma samples (1, nodakenin; 2, decursinol; 3, IS; 4, decursin; and 5, decursinol angelate). (A) blank human plasma, (B) human plasma spiked with the four coumarins at LLOQ of 0.05 ng/mL and IS (10 ng/mL), (C) human plasma taken at 1 h after the usual oral dose administration of 4.6 g of AGN root extract powder containing 0.055 mg of D, 0.184 mg of DA, and 1.095 mg of nodakenin.
Figure 4
Figure 4
Mean plasma concentration–time profiles of four coumarins after oral administration of AGN root extract powder (4.6 g) in humans (Mean ± SE, n = 10).

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References

    1. Sarker D.S., Lahar N. Natural medicine: The genus Angelica. Curr. Med. Chem. 2004;11:1479–1500. doi: 10.2174/0929867043365189. - DOI - PubMed
    1. Zhang J., Li L., Jiang C., Xing C., Kim S.H., Lu J. Anti-cancer and other bioactivities of Korean Angelica gigas Nakai (AGN) and its major pyranocoumarin compounds. Anti-Cancer Agents Med. Chem. 2012;12:105–109. doi: 10.2174/187152012803833071. - DOI - PubMed
    1. Ahn K.S., Sim W.S., Kim I.H. Detection of Anticancer Activity from the Root of Angelica gigas In Vitro. J. Microbiol. Biotechnol. 1995;5:1239–1254.
    1. Lee H.J., Lee H.J., Lee E.O., Lee J.H., Lee K.S., Kim K.H., Kim S.H., Lu J. In vivo anti-cancer activity of Korean Angelica gigas and its major pyranocoumarin decursin. Am. J. Chin. Med. 2009;37:127–142. doi: 10.1142/S0192415X09006722. - DOI - PubMed
    1. Kang S.Y., Kim Y.C. Neuroprotective coumarins from the root of Angelica gigas: Structure-activity relationships. Arch. Pharm. Res. 2007;30:1368–1373. doi: 10.1007/BF02977358. - DOI - PubMed

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