Abstract
Purpose
The purpose of this study was to develop a sensitive method for quantifying cinnamic acid in human plasma using UPLC–ESI–MS/MS.
Methods
Cinnamic acid was separated using water containing 0.005% (v/v) formic acid and acetonitrile as a mobile phase by gradient elution at a flow rate 0.2 mL/min, equipped with a HALO-C18 column (2.1 × 100 mm, 2.7 μm). Quantitation of this analysis was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in multiple reaction monitoring negative ion mode. The mass transitions were m/z 146.8 → 103.0 for cinnamic acid, and 432.9 → 225.0 for geniposide as internal standard. Liquid–liquid extraction and protein precipitation with ethyl acetate–methanol-1.2% acetic acid (4/16/1, v/v/v) were used in the sample extraction.
Results
The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma constituents. The calibration curves for cinnamic acid in human plasma were 0.1–500 ng/mL and displayed excellent linearity with correlation coefficients (r) greater than 0.99. Both the intra- and inter-day precisions (CV%) were within 3.88% for human plasma. The accuracy was 99.34–106.69% for human plasma. In vitro plasma protein binding of cinnamic acid was 64.26 ± 1.89 and 65.50 ± 1.78% for the spiked human plasma concentrations of 100 and 1000 ng/mL, respectively.
Conclusion
The developed analytical method satisfied the criteria of international guidance and could be successfully applied to the pharmacokinetic study of cinnamic acid after oral administration of Socheongryong-tang tablets to humans.
Similar content being viewed by others
References
Basu S, Jana S, Patel VB, Patel H (2013a) Effects of piperine, cinnamic acid and gallic acid on rosuvastatin pharmacokinetics in rats. Phytother Res 27:1548–1556
Basu S, Patel VB, Jana S, Patel H (2013b) Liquid chromatography tandem mass spectrometry method (LC–MS/MS) for simultaneous determination of piperine, cinnamic acid and gallic acid in rat plasma using a polarity switch technique. Anal Methods 5:967–976
Chen Y, Ma Y, Ma W (2009) Pharmacokinetics and bioavailability of cinnamic acid after oral administration of ramulus cinnamomi in rats. Eur J Drug Metab Pharmacokinet 34:51–56
FDA (2018) Bioanalytical method validation guidance for industry. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM), Rockville
Gao X, Yu Z, Zhao Y, Men L, Wang Q, Wang Z, Chen X, Xiao W, Bi K (2009) Development of an LC method for simultaneous analysis of cinnamic acid and paeonol in rat plasma, and its application to a pharmacokinetic study after intragastric administration of Guizhi-Fuling capsule. Chromatographia 70:597–601
Gao Y, Wu J, Jiang R, Zhao G (2011) Determination of cinnamic acid and glycyrrhizic acid in rat serum and its pharmacokinetics after oral administration of Dangguisini decoction. J Chin Med Mater 34:408–411
Goudah A, Hasabelnaby S (2010) Pharmacokinetics, plasma protein binding and bioavailability of moxifloxacin in Muscovy ducks after different routes of administration. Res Vet Sci 88:507–511
Ikeda Y, Kaneko A, Yamamoto M, Ishige A, Sasaki H (2002) Possible involvement of suppression of Th2 differentiation in the anti-allergic effect of sho-seiryu-to in mice. Jpn J Pharmacol 90:328–336
Jeong S-H, Jang J-H, Ham S-H, Yang S-J, Cho H-Y, Lee Y-B (2018) Simultaneous UPLC-MS/MS determination of four components of Socheongryong-tang tablet in human plasma: application to pharmacokinetic study. J Chromatogr B 1095:214–225
Ji B, Zhao Y, Zhang Q, Wang P, Guan J, Rong R, Yu Z (2015) Simultaneous determination of cinnamaldehyde, cinnamic acid, and 2-methoxy cinnamic acid in rat whole blood after oral administration of volatile oil of Cinnamoni Ramulus by UHPLC-MS/MS: an application for a pharmacokinetic study. J Chromatogr B 1001:107–113
Kao ST, Wang ST, Yu CK, Lei HY, Wang JY (2000) The effect of chinese herbal medicine, xiao-qing-long tang (XQLT), on allergen-induced bronchial inflammation in mite-sensitized mice. Allergy 55:1127–1133
Kao ST, Lin CS, Hsieh CC, Hsieh WT, Lin JG (2001) Effects of xiao-qing-long-tang (XQLT) on bronchoconstriction and airway eosinophil infiltration in ovalbumin-sensitized guinea pigs: in vivo and in vitro studies. Allergy 56:1164–1171
Lee CW, An WG (2011) Single dose toxicity study of socheongryong-tang in sprague-dawley rats. J Physiol Pathol Korean Med 25:242–245
Li K, Bi K (2006) RP-HPLC determination and pharmacokinetic comparison of cinnamic acid in rat plasma after administration of Di-Gu-Pi decoction and pure cinnamic acid. Chem Res Chin Univ 22:56–60
Li P, Zhang Y, Xiao L, Jin X, Yang K (2007) Simultaneous determination of harpagoside and cinnamic acid in rat plasma by high-performance liquid chromatography: application to a pharmacokinetic study. Anal Bioanal Chem 389:2259–2264
Liang M-T, Yang C-H, Li S-T, Yang C-S, Chang H-W, Liu C-S, Cham T-M, Chuang L-Y (2008) Antibacterial and antioxidant properties of Ramulus Cinnamomi using supercritical CO2 extraction. Eur Food Res Technol 227:1387–1396
Lin J, Xu L-Z, Liu J-Y, Zou Z-M (2005) Study on contents of cinnamaldehyde and cinnamic acid and distribution of Ramulus Cinnamomi. Chin Pharm J 40:1784
Liu L, Hudgins WR, Shack S, Yin MQ, Samid D (1995) Cinnamic acid: a natural product with potential use in cancer intervention. Int J Cancer 62:345–350
Lu W, Gao S, Xiao Y, Zhang L, Li J, Chen W (2011) A liquid chromatographic-tandem mass spectrometric method for the quantitation of eight components involved in lithospermic acid B biosynthesis pathway in Salvia miltiorrhiza hairy root cultures. J Med Plant Res 5:1664–1672
Song Z, Bi K, Luo X (2002) An HPLC method for the determination and pharmacokinetic study of cinnamic acid in the plasma of rats having taken the traditional Chinese medicinal preparation Ling-Gui-Zhu-Gan decoction. J Chromatogr Sci 40:198–200
Urien S, Tillement J-P, Barré J (2001) The significance of plasma-protein binding in drug research. Wiley, Zürich
Wang R, Sun T, Jing D, Chen X, Yu Z, Bi K (2005) High performance liquid chromatographic determination of cinnamic acid in rabbit plasma and application in study of pharmacokinetics. Chin J Chromatogr 23:273–275
Wang S-J, Ruan J-X, Zhao Y-H, Zhang Z-Q (2008) Simultaneous determination of harpagoside and cinnamic acid in rat plasma by liquid chromatography electrospray ionization mass spectrometry and its application to pharmacokinetic studies. Biomed Chromatogr 22:50–57
Wu T, Zhang J, Tan H-S, Ju W-Z, Xu X-Y (2014) Determination of plasma concentration of five phenolic acid by LC-MS/MS and study of pharmacokinetics in rats after Mailuoning injection. J Chin Med Mater 39:1928–1932
Xiong Z, Fu Y, Li J, Qin F, Li F (2010) A UPLC–MS–MS method for quantification of harpagoside and cinnamic acid in rat plasma and its application to a pharmacokinetic study after oral administration of Yanyan tablets. Chromatographia 72:163–169
Yang C, Hou S, Sun Y, Li C (2001) Pharmacokinetics of cinnamic acid of BAOXIN PILL in rat. Chin Tradit Herbal Drugs 32:616–618
Zhang J, Chen M, Ju W, Liu S, Xu M, Chu J, Wu T (2010) Liquid chromatograph/tandem mass spectrometry assay for the simultaneous determination of chlorogenic acid and cinnamic acid in plasma and its application to a pharmacokinetic study. J Pharm Biomed Anal 51:685–690
Zhao G, Peng C, Du W, Wang S (2014) Simultaneous determination of imperatorin and its metabolites in vitro and in vivo by a GC-MS method: application to a bioavailability and protein binding ability study in rat plasma. Biomed Chromatogr 28:947–956
Acknowledgements
This work was supported by a Grant of the National Development Institute of Korean Medicine (NIKOM) funded by the Korean Ministry of Health and Welfare (MOHW), Republic of Korea.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Ethical approval
The Institutional Review Board of Dongshin Oriental Medicine Hospital (IRB approval number: 2017-02, Suncheon, Republic of Korea) approved the study protocol. This study was carried out according to the revised Declaration of Helsinki for biomedical research involving human subjects and the rules of Good Clinical Practice. The subjects were provided written informed consent prior to participation. All received a physical examination, medical history taking, and laboratory tests. Each participant was sufficiently healthy for inclusion.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Jeong, SH., Jang, JH., Cho, HY. et al. A sensitive UPLC–ESI–MS/MS method for the quantification of cinnamic acid in vivo and in vitro: application to pharmacokinetic and protein binding study in human plasma. J. Pharm. Investig. 50, 159–172 (2020). https://doi.org/10.1007/s40005-019-00444-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40005-019-00444-0