Simultaneous determination of the pharmacokinetics of the active components of San-Chen-pill by UPLC-Q-Exactive-MS

doi:10.5246/jcps.2019.11.077

Abstract

Abstract:

In the present study, we developed a rapid, sensitive and efficient ultra high-performance liquid chromatography-tandemmass spectrometric (UPLC-Q-Exactive-MS) method, and six bioactive constituents in San-Chen-pill (SCP), including cholic acid (CA),hyodeoxycholic acid (HDCA), hydroxysafflor yellow A (HSYA), kaempferol-3-O-rutinoside (KFR), anhydrosafflor yellow B (AHSYB) and syringin (SRG), in rat plasma after oral administration of San-Chen-pill, were simultaneously determined. Plasma samples were pretreated with methanol for protein precipitation. Chromatography separation was performed on a SHIMADZU of shim-pack GIST C₁₈ column using a gradient mobile phase consisting of acetonitrile and 0.1% formic acid aqueous solution. A tandem mass spectrometric detection with an electrospray ion source (HESI) interface was conducted in negative ionization mode. For all the six analytes of interest, the calibration curves were linear within the concentration rage of 0.50–1280 ng/mL with r≥0.99. The intra-day and inter-day precisions (in terms of relative standard deviation, RSD) were all below 12.7% for all six analytes. Extraction recovery, matrix effect and stability data all met the acceptance criteria of FDA guideline for bioanalytical method validation. In addition, San-Chen-pill is a traditional Mongolian herbal medicine that has been prepared with three medicinal herbs,Calculus bovis, Carthamus tinctorius L. and Concretio silicea bambusae, and it shows potent anti-anginal activity in all preparationswith in a ratio of 1:1:1. The pharmacokinetic parameters of San-Chen-pill were reported herein for the first time, and this developed method was successfully used in a pharmacokinetic study for San-Chen-pill.

Key words: San-Chen-pill, Pharmacokinetics, UPLC-Q-Exactive-MS

CLC Number:

R944

Supporting:

Lingling Zhang, Huiwen Zhang, Shikui Wu, Hong Liu, Jingyuan Li, Xin Dong, Huimin Xia, Huanyun Wang. Simultaneous determination of the pharmacokinetics of the active components of San-Chen-pill by UPLC-Q-Exactive-MS[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(11): 812-824.

References

[1] Ministry of health pharmacopoeia committee. Ministry of health of the People’s Republic of China drug standards- Mongolian medicine standards. 1988, 59.

[2] Peng, C.; Tian, J.X.; Lv, M.; Huang, Y.; Tian, Y.; Zhang, Z.J. Development and validation of a sensitive LC-MS-MS method for the simultaneous determination of multicomponent contents in artificial Calculus Bovis. J. Chromatogr. Sci. 2014, 52, 128-136.

[3] Chang, Z.R.; Di, F.; Zhou, F.R. Study on determination of cholic acid in natural bezoar by TLC chromatography. China J. Tradit. Chin. Med. 1999, 24, 684.

[4] Zhan, R.M.; Cui, F.M.; Wang, A.M.; et al. In vitro cultivate of cholic acid and its components in wild boar. Chin. Herb. Med. 1995, 26, 592.

[5] Zhang, X.H.; Zheng, W.; Xu, H.L.; Huang, X.; Ren, P.; Zou, H.; Liu, G.H.; Wang, J.; Ma, X.L. Pharmacokinetic study of representative anti-oxidative compounds from Denshen-Chuanxiong-Honghua following oral administration in rats. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2017, 1052, 82-90.

[6] Jin, Y.; Tang, Y.P.; Zhu, Z.H.; Shang, E.X.; Pang, H.Q.; Shi, X.Q.; Chen, Y.Y.; Wang, J.; Chang, X.; Kang, A.; Zhou, G.S.; Shi, Y.J.; Sun, J.; Tang, Z.S.; Li, S.P.; Duan, J.N. Pharmacokinetic comparison of seven major bio-active components in normal and blood stasis rats after oral administration of herb pair danggui-honghua by UPLC-TQ/MS. Molecules. 2017, 22, E1746.

[7] Li, F.; He, Z.S.; Ye, Y. Flavonoids from carthamus tinctorius. Chin. J. Chem. 2010, 20, 699-702.

[8] Zhou, X.D.; Tang, L.Y.; Xu, Y.L.; Zhou, G.H.; Wang, Z.J. Towards a better understanding of medicinal uses of Carthamus tinctorius L. in traditional Chinese medicine: a phytochemical and pharmacological review. J. Ethnopharmacol. 2014, 151, 27-43.

[9] Zan, T.; Piao, L.; Wei, Y.T.; Gu, Y.; Liu, B.H.; Jiang, D.Q. Simultaneous determination and pharmacokinetic study of three flavonoid glycosides in rat plasma by LC-MS/MS after oral administration of Rubus chingii Hu extract. Biomed. Chromatogr. 2018, 32.

[10] Liang, S.P.; Liu, F.; Du, F.F.; Niu, W.; Sun, Y.; Li, C.; Guo, M.L. A new method for determination of kaempferol-3-O-rutinoside in plasma: Application to pharmacokinetic study in Sprague-Dawley rats. Chin. J. Clin. Pharmacol. Therap. 2006, 11, 491-49

[11] Liu, R.; Ma, R.; Yu, C.Y.; Bi, C.W.; Yin, Y.D.; Xu, H.R.; Shang, H.W.; Bi, K.S.; Li, Q. Quantitation of eleven active compounds of Aidi injection in rat plasma and its application to comparative pharmacokinetic study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2016, 1026, 105-113.

[12] Guideline on Bioanalytical Method Validation. http://www.ema.europa.eu/docs/en GB/document library/Scientific guideline/2011/08/WC500109686.

[13] Sun, Y.W.; He, Y.; Liu, W.H.; Xiang, H.; Tang, Y.H.; Jin, Z. Study on pharmacokinetics of hydroxysafflor yellow A and anhydrosafflor yellow B from safflower extract in rats. China J. Tradit. Chin.Med. Pharm. 2015, 30, 4287-4291.

[14] Shi, X.H.; Tang, Y.H.; Chen, J.Z.; Shi, S.L.; He, Y. Pharmacokinetics of hydroxysafflor yellow A in Guhong Injection in rats. Chin. Tradit. Pat. Med. 2015, 37, 2387-2391.

[15] Qi, J.P.; Jin, X.F.; Huang, L.S.; Ping, Q.N. Simultaneous determination of hydroxysafflor yellow A and ferulic acid in rat plasma after oral administration of the co-extractum of Rhizoma chuanxiong and Flos Carthami by HPLC-diode array detector. Biomed. Chromatogr. 2007, 21, 816-822.

[16] Zhao, L.; Qian, X.; Li, W.H.; Lv, L.; Zhang, H.; Chai, Y.F.; Zhang, G.Q. An LC-MS/MS method for the simultaneous determination and pharmacokinetic studies of bergenin, chlorogenic acid and four flavonoids in rat plasma after oral administration of a QingGanSanJie decotion extract. Biomed. Chromatogr. 2014, 28, 1670-1678.

[17] Kim, M.J.; Kwon, S.H.; Jang, C.G.; Maeng, H.J. Determination of isoorientin levels in rat plasma after oral administration of Vaccinum bracteatum Thunb. methanol extract by high-performance liquid chromatography-tandem mass spectrometry. Biomed. Chromatogr. 2018, 32, e4188.

[18] Wang, Y.J.; Wen, J.; Zheng, W.H.; Zhao, L.S.; Fu, X.H.; Wang, Z.Z.; Xiong, Z.L.; Li, F.M.; Xiao, W. Simultaneous determination of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and geniposide in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after administration of Reduning injection. Biomed. Chromatogr. 2015, 29, 68-74.

[19] Hofmann, A.F.; Cravetto, C.; Molino, G.; Belforte, G.; Bona, B. Simulation of the metabolism and enterohepatic circulation of endogenous deoxycholic acid in humans using a physiologic pharmacokinetic model for bile acid metabolism. Gastroenterology. 1987, 93, 693-709.

[20] Tian, Y.; Yang, Z.F.; Li, Y.; Qiao, Y.; Yang, J.; Jia, Y.Y.; Wen, A.D. Pharmacokinetic comparisons of hydroxysafflower yellow A in normal and blood stasis syndrome rats. J. Ethnopharmacol. 2010, 129, 1-4.

[21] Tian, Z.M. The development of blood concentration measurement on the syndrome of Chinese formula and efficacy determination. Foreign Med. Sci. 1989, 10, 58-59.