Abstract
Background: It is urgently needed to clarify the pharmacokinetic mechanism for the multibioactive constituents in Traditional Chinese Medicines for its clinical applications. A rapid, sensitive and reliable ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of Danshensu, Ferulic acid, Astragaloside IV, Naringin, Neohesperidin and Puerarin after oral administration of Naoshuantong Granule using Carbamazepine as internal standard (IS).
Methods: The plasma samples were pretreated by liquid-liquid extraction method using ethyl acetate after acidification, and separated on a Waters ACQUITY UPLC® BEH C18 column (50×2.1 mm, i.d., 1.7 µm) by gradient elution with a mobile phase composing of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.2 mL/min. Multiple reaction monitoring (MRM) mode with both positive and negative ion mode was operated using an electrospray ionization (ESI) to detect the six compounds.
Result: All calibration curves showed good linearity (r>0.99) over a wide concentration range. The intra- and inter-day precision (RSD%) was below 8.4% and the accuracy (RE%) ranged from 91.1% to 107.5%. The extraction recoveries of the six analytes and IS in the plasma were more than 77.9% and no severe matrix effect was observed.
Conclusion: The fully validated method was successfully applied to the pharmacokinetics of Naoshuantong Granule.
Keywords: UPLC-MS/MS, naoshuantong granule, danshensu, ferulic acid, rat plasma, pharmacokinetics.
Graphical Abstract
[1]
Li, Z.H.; Xiao, S.; Ai, N.K. Luo, Fan; X.H.; Cheng, Y. Derivative, multiple reaction monitoring and single herb calibration approach for multiple components quantification of traditional Chinese medicine analogous formulae. J. Chromatogr. A, 2015, 1376(1), 126-142.
[2]
Li, P.; Qi, L.W.; Liu, E.H.; Zhou, J.L.; Wen, X.D. Analysis of Chinese herbal medicines with holistic approachesand integrated evaluation models. Trends Analyt. Chem., 2008, 27(1), 66-77.
[3]
Huang, X.; Kong, L.; Li, X.; Chen, X.; Guo, M.; Zou, H. Strategy for analysis and screening of bioactive compounds in traditional Chinese medicines. J. Chromatogr. B., 2004, 812(1-2), 71-84.
[4]
Song, X.Y.; Li, Y.D.; Shi, Y.P.; Jin, L.; Chen, J. Quality control of traditional Chinese medicines: a review. Chin. J. Nat. Med., 2013, 11(6), 596-607.
[5]
Lam, F.F.Y.; Yeung, J.H.K.; Chan, K.M.; Or, P.M.Y. Relaxant effects of danshen aqueous extract and its constituent danshensu on rat coronary artery are mediated by inhibition of calcium channels. Vascul. Pharmacol., 2007, 46(4), 271-277.
[6]
Li, Y.; Bi, K. HPLC determination of ferulic acid in rat plasma after oral administration of Rhizoma Chuanxiong and its compound preparation. Biomed. Chromatogr., 2003, 17(8), 543-546.
[7]
Zhao, K.J.; Dong, T.T.; Tu, P.F.; Song, Z.H.; Lo, C.K.; Tsim, K.W. Molecular genetic and chemical assessment of Radix Angelica (Danggui) in China. J. Agr. Food Chem., 2003, 51(9), 2576-2583.
[8]
Hong, Q.; Ma, Z.C.; Huang, H.; Wang, Y.G.; Tian, H.L.; Xiao, C.R.; Liang, Q.D.; Zhang, H.T.; Gao, Y. Antithrombotic activities of ferulic acid via intracellular cyclic nucleotide signaling. Eur. J. Pharmacol., 2016, 777(8), 1-8.
[9]
Auyeung, K.K.; Woo, P.K.; Law, P.C.; Ko, J.K. Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells. J. Ethnopharmacol., 2012, 141(2), 635-641.
[10]
Chen, X.J.; Meng, D.; Feng, L.; Bian, Y.Y.; Li, P.; Yang, D.; Cao, K.J.; Zhang, J.N. Protective effect of astragalosides on myocardial injury by isoproterenol in SD rats. J. Chinese. Med., 2006, 34(6), 1015-1025.
[11]
Chanet, A.; Milenkovic, D.; Deval, C.; Potier, M.; Constans, J.; Mazur, A.; Pelissero, C.B.; Morand, C.; Bérard, A.M. Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice. J. Nutr. Biochem., 2012, 23(5), 469-477.
[12]
Iranshahia, M.; Rezaee, R.; Parhiz, H.; Roohbakhsh, A.; Soltani, F. Protective effects of flavonoids against microbes and toxins: The cases of hesperidin and hesperetin. Life Sci., 2015, 137(9), 125-132.
[13]
Jain, M.; Parmar, H.S. Evaluation of antioxidative and anti-inflammatory potential of hesperidin and naringin on the rat air pouch model of inflammation. Inflamm. Res., 2010, 60(5), 483-491.
[14]
Choo, M.K.; Park, E.K.; Yoon, H.K.; Kim, D.H. Antithrombotic and antiallergic activities of daidzein, a metabolite of puerarin and daidzin produced by human intestinal microflora. Biol. Pharm. Bull., 2002, 25(10), 1328-1332.
[15]
Zheng, L.; Gong, Z.; Lu, Y.; Xie, Y.; Huang, Y.; Liu, Y.; Lan, Y.; Wang, A.; Wang, Y.A. UPLC-MS/MS method for simultaneous determination of danshensu, protocatechuic aldehyde, rosmarinic acid, and ligustrazine in rat plasma, and its application to pharmacokinetic studies of Shenxiong glucose injection in rats. J. Chromatogr. B., 2015, 997(2015), 210-217.
[16]
Sun, X.; Zhang, P.; Wu, X.; Wu, Q.; Zhang, M.; An, Y.; Shi, G. Simultaneous determination of calycosin-7-O-β-D-glucoside, calycosin, formononetin, astragaloside IV and schisandrin in rat plasma by LC-MS/MS: application to a pharmacokinetic study after oral administration of Shenqi Wuwei chewable tablets. Biomed. Chromatogr., 2014, 28(8), 1118-1125.
[17]
Jin, Y.; Tian, T.; Ma, Y.; Xu, H.; Du, Y. Simultaneous determination of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Weifuchun tablet. J. Chromatogr. B, 2015, 1000(9), 112-119.
[18]
Guo,, X.; Chen, X.; Li, Y.; Shen, Z.; Wang, X. Zheng, P.; Duan, F.; Ma, Y.; Bi, K. LC-MS determination and pharmacokinetic study of six phenolic components in rat plasma after taking traditional Chinese medicinaln-preparation: Guanxinning lyophilized powder for injection. J. Chromatogr. B, 2008, 873(1), 51-58.
[19]
Yan, B.; Xing, D.; Ding, Y.; Tao, J.; Du, L. HPLC method for the determination and pharmacokinetic studies on puerarin in cerebral ischemia reperfusion rat plasma after intravenous administration of puerariae radix isoflavone. J. Pharm. Biomed. Anal., 2005, 37(2), 297-301.
[20]
Liang, X.; Tian, J.; Li, L.; Gao, J.; Zhang, Q.; Gao, P.; Song, S. Rapid determination of eight bioactive alkaloids in Portulaca oleracea L. by the optimal microwave extraction combined with positive-negative conversion multiple reaction monitor (+/-MRM) technology. Talanta, 2014, 120(3), 167-172.
[21]
Chen, L.; Liu, Y.; Jia, D.; Yang, J.; Zhao, J.; Chen, C.; Liu, H.; Liang, X. Pharmacokinetics and Biodistribution of Aurantiamide and Aurantiamide Acetate in Rats after Oral Administration of Portulaca oleracea L. Extracts. J. Agric. Food Chem., 2016, 64(17), 3445-3455.
[22]
Gao, H.; Wang, Z.; Li, Y.; Qian, Z. Overview of the quality standard research of traditional Chinese medicine. Front. Med., 2011, 5(2), 195-202.
[23]
Jing, J.; Ren, W.C.; Chen, S.B.; Wei, M.; Parekh, H.S. Advances in analytical technologies to evaluate the quality of traditional Chinese medicines. Trends Analyt. Chem., 2013, 44(44), 39-45.
[24]
Jin, H.; Liu, Y.; Guo, Z.; Wang, J.; Zhang, X.; Wang, C.; Liang, X. Recent development in liquid chromatography stationary phases for Separation of Traditional Chinese Medicine components. J. Pharm. Biomed. Anal., 2016, 130(10), 336-346.
[25]
Wang, X.; Zhang, A.; Yan, G.; Han, Y.; Sun, H. UHPLC-MS for the analytical characterization of traditional Chinese medicines. Trends Analyt. Chem., 2014, 63(12), 180-187.
[26]
Duan, K.; Yuan, Z.; Guo, W.; Meng, Y.; Cui, Y.; Kong, D.; Zhang, L.; Wang, N. LC-MS/MS determination and pharmacokinetic study of five flavone components after solvent extraction/acid hydrolysis in rat plasma after oral administration of Verbena officinalis L. extract. J. Ethnopharmacol., 2011, 135(2), 201-208.
[27]
Li, W.; Li, Z.W.; Han, J.P.; Li, X.X.; Gao, J.; Liu, C.X. Determination and pharmacokinetics of danshensu in rat plasma after oral administration of danshen extract using liquid chromatography/tandem mass spectrometry. Eur. J. Drug Metab. Pharmacokinet., 2008, 33(1), 9-16.
[28]
Wang, S.P.; Liu, L.; Wang, L.L.; Jiang, P.; Xiang, L.; Zhang, W.D. Simultaneous determination of six hydrophilic components in rat plasma after oral administration of Jitai tablet by liquid chromatography-electrospray ionization-tandem mass spectrometry: Application to a pharmacokinetic study. J. Chromatogr. B, 2013, 912(1), 75-84.
[29]
Li, N.; Liu, C.; Mi, S.; Wang, N.; Zheng, X.; Li, Y.; Huang, X.; He, S.; Chen, H.; Xu, X.H. Simultaneous determination of oleanolic acid, p-coumaric acid, ferulic acid, kaemperol and quercetin in rat plasma by lc-ms-ms and application to a pharmacokinetic study of oldenlandia diffusa extract in rats. J. Chromatogr. Sci., 2012, 50(10), 885-892.
[30]
Chen, J.; Chen, Z.; Ma, L.; Liang, Q.; Jia, W.; Pan, Z.; Zeng, Y.; Jiang, B. Development of determination of four analytes of Zhi-Shao-San decoction using LC-MS/MS and its application to comparative pharmacokinetics in normal and irritable bowel syndrome rat plasma. Biomed. Chromatogr., 2014, 28(10), 1384-1392.
[31]
Wen, J.; Qiao, Y.; Yang, J.; Liu, X.; Song, Y.; Liu, Z.; Li, F. UPLC-MS/MS determination of paeoniflorin, naringin, naringenin and glycyrrhetinic acid in rat plasma and its application to a pharmacokinetic study after oral administration of Si Ni San decoction. J. Pharm. Biomed. Anal., 2012, 66(7), 271-277.
[32]
Hu, D.D.; Han, Q.B.; Zhong, L.L.; Li, Y.H.; Lin, C.Y.; Ho, H.M.; Zhang, M.; Lin, S.H.; Zhao, L.; Huang, T.; Mi, H.; Tan, H.S.; Xu, H.X.; Bian, Z.X. Simultaneous determination of ten compounds in rat plasma by UPLC-MS/MS: Application in the pharmacokinetic study of Ma-Zi-Ren-Wan. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2015, 1000(9), 136-146.
[33]
Tong, L.; Zhou, D.; Gao, J.; Zhu, Y.; Sun, H.; Bi, K. Simultaneous determination of naringin, hesperidin, neohesperidin, naringenin and hesperetin of Fractus aurantii extract in rat plasma by liquid chromatography tandem mass spectrometry. J. Pharm. Biomed. Anal., 2012, 58(2), 58-64.
[34]
Huang, C.; Wang, G.; Li, H.; Xie, H.; Sun, J.; Lv, H.; Lv, T. Sensitive and selective liquid chromatography-electrospray ionisation-mass spectrometry analysis of astragaloside-IV in rat plasma. J. Pharm. Biomed. Anal., 2006, 40(3), 788-793.
[35]
Zhao, X.; Zhao, Y.L.; Liu, X.M.; Han, W.; Yu, Z.G. Simultaneous determination of six isoflavonoids in rat plasma after administration of total flavonoid from Gegen by ultra-HPLC-MS/MS. J. Sep. Sci., 2012, 35(8), 984-993.
[36]
Yan, Y.; Chai, C.Z.; Wang, D.W.; Wu, J.; Xiao, H.H.; Huo, L.L.; Zhu, D.N.; Yu, B.Y. Simultaneous determination of puerarin, daidzin, daidzein, paeoniflorin, albiflorin, liquiritin and liquiritigenin in rat plasma and its application to a pharmacokinetic study of Ge-Gen Decoction by a liquid chromatography-electrospray ionization-tandem mass spectrometry. J. Pharm. Biomed. Anal., 2014, 95(3), 76-84.
Article Metrics
31
3
1