Volume 12 Issue 4
Sep.  2022
Turn off MathJax
Article Contents
Xuan Yu, Wei Niu, Ya-Ya Wang, Olajide E. Olaleye, Jia-Nan Wang, Meng-Yuan Duan, Jun-Ling Yang, Rong-Rong He, Zi-Xuan Chu, Kai Dong, Gui-Ping Zhang, Chang-Xiao Liu, Chen Cheng, Chuan Li. Novel assays for quality evaluation of XueBiJing: Quality variability of a Chinese herbal injection for sepsis management[J]. Journal of Pharmaceutical Analysis, 2022, 12(4): 664-682. doi: 10.1016/j.jpha.2022.01.001
Citation: Xuan Yu, Wei Niu, Ya-Ya Wang, Olajide E. Olaleye, Jia-Nan Wang, Meng-Yuan Duan, Jun-Ling Yang, Rong-Rong He, Zi-Xuan Chu, Kai Dong, Gui-Ping Zhang, Chang-Xiao Liu, Chen Cheng, Chuan Li. Novel assays for quality evaluation of XueBiJing: Quality variability of a Chinese herbal injection for sepsis management[J]. Journal of Pharmaceutical Analysis, 2022, 12(4): 664-682. doi: 10.1016/j.jpha.2022.01.001

Novel assays for quality evaluation of XueBiJing: Quality variability of a Chinese herbal injection for sepsis management

doi: 10.1016/j.jpha.2022.01.001
Funds:

This work was funded by grants from the National Natural Science Foundation of China (Grant Nos.: 82074176 and 81503345), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (Grant No.: ZYYCXTD-C-202009), and the National Key R&

D Program of China (Grant No.: 2018YFC1704500).

  • Received Date: Aug. 27, 2021
  • Accepted Date: Jan. 21, 2022
  • Rev Recd Date: Jan. 04, 2022
  • Publish Date: Jan. 26, 2022
  • XueBiJing is an intravenous five-herb injection used to treat sepsis in China. The study aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS)- or liquid chromatography-ultraviolet (LC-UV)-based assay for quality evaluation of XueBiJing. Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point calibrator for monitoring the various analytes in parallel. Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition, pharmacokinetics, and pharmacodynamics. A selectivity test (for "similarity of response") was developed to identify and minimize interference by non-target constituents. Then, an intercept test was developed to fulfill "linearity through zero" for each analyte (absolute ratio of intercept to C response, <2%). Using the newly developed assays, we analyzed samples from 33 batches of XueBiJing, manufactured over three years, and found small batch-to-batch variability in contents of the marker constituents (4.1%-14.8%), except for senkyunolide I (26.5%).
  • loading
  • National People's Congress Standing Committee, Drug Administration Law of the People's Republic of China, Law Press·China, 2019
    National Medical Products Administration, The notification regarding the implementation of Good Manufacturing Practice of Medical Products (version 2010), https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20110225152101646.html. (Accessed 28 June 2021)
    Chinese Pharmacopoeia Commission, Pharmacopoeia of the People's Republic of China, Beijing, China Medical Science Press, Beijing, 2020
    C.-X. Liu, S.-L. Chen, X.-H. Xiao, et al., A new concept on quality marker of Chinese materia medica:quality control for Chinese medicinal products, Chin. Tradit. Herb. Drugs 47 (2016) 1443-1457
    C.-X. Liu, Y.-Y. Cheng, D.-A. Guo, et al., A new concept on quality marker for quality assessment and process control of Chinese medicines, Chin. Herb. Med. 9 (2017) 3-13
    W. Yang, Y. Zhang, W. Wu, et al., Approaches to establish Q-markers for the quality standards of traditional Chinese medicines, Acta Pharm. Sin. B 7 (2017) 439-446
    J. He, X. Feng, K. Wang, et al., Discovery and identification of quality markers of Chinese medicine based on pharmacokinetic analysis, Phytomedicine 44 (2018) 182-186
    T. Zhang, G. Bai, Y. Han, et al., The method of quality marker research and quality evaluation of traditional Chinese medicine based on drug properties and effect characteristics, Phytomedicine 44 (2018) 204-211
    C. Liu, D.-A. Guo, L. Liu, Quality transitivity and traceability system of herbal medicine products based on quality markers, Phytomedicine 44 (2018) 247-257
    D. Wang, Q. Li, R. Liu, et al., Quality control of Semen Ziziphi Spinosae standard decoction based on determination of multi-components using TOF-MS/MS and UPLC-PDA technology, J. Pharm. Anal. 9 (2019) 406-413
    M. Singer, C.S. Deutschman, C.W. Seymour, et al., The third international consensus definitions for sepsis and septic shock (sepsis-3), JAMA 315 (2016) 801-810
    Y. Song, C. Yao, Y. Yao, et al., XueBiJing injection versus placebo for critically ill patients with severe community-acquired pneumonia:a randomized controlled trial, Crit. Care Med. 47 (2019) e735-e743
    G. Chen, Y. Gao, Y. Jiang, et al., Efficacy and safety of XueBiJing injection combined with ulinastatin as adjunctive therapy on sepsis:a systematic review and meta-analysis, Front. Pharmacol. 9 (2018), 743
    C. Li, P. Wang, L. Zhang, et al., Efficacy and safety of XueBiJing injection (a Chinese patent) for sepsis:a meta-analysis of randomized controlled trials, J. Ethnopharmacol. 224 (2018) 512-521
    Y. Chen, C.-S. Li, The effectiveness of XueBiJing injection in therapy of sepsis:a multicenter clinical study, Chin. J. Emerg. Med. 22 (2013) 130-135
    J. Gao, L. Kong, S. Liu, et al., A prospective multicenter clinical study of XueBiJing injection in the treatment of sepsis and multiple organ dysfunction syndrome, Chin. Crit. Care Med. 27 (2015) 465-470
    Chinese National Health Commission and Chinese State Administration of Traditional Chinese Medicine, Diagnosis and Treatment of Adults with Coronavirus Disease 2019 (COVID-19) (the revised 8th version), http://www.gov.cn/zhengce/zhengceku/2021-04/15/5599795/files/e9ce837932e6434db998bdbbc5d36d32.pdf. (Accessed 28 June 2021)
    National Medical Products Administration, Chinese national drug standard (Guojia Yaopin Biaozhun) of XueBiJing injection (YBZ01242004-2010Z-2012), http://ypbz.cnjournals.com/ch/reader/view_abstract.aspx?file_no=20130618&flag=1. (Accessed 28 June 2021)
    Y. Chen, Y. Li, X. Chen, et al., Development and validation of a HPLC method for the determination of five bioactive compounds in the "XueBiJing" injection, Anal. Lett. 43 (2010) 2456-2464
    L.-X. Ji, H. Huang, M. Jiang, et al., Simultaneous HPLC determination of 11 essential compounds in XueBiJing injection, China J. Chin. Mater. Med. 35 (2010) 2395-2398
    Y.-H. Zhang, W.-W. Hu, S.-J. Ren, et al., Simultaneous Determination of Multicomponent in XueBiJing by HPLC, Chin. J. Spectrosc. Lab. 30 (2013) 2305-2308
    H. Huang, J. Wang, J.Z. Fu, et al., Simultaneous determination of thirteen main components and identification of eight major metabolites in XueBiJing injection by UPLC/Q-TOF, J. Anal. Chem. 68 (2013) 348-356
    Z. Sun, J.-T. Fu, L. Zhou, et al., Simultaneous determination of eight constituents in XueBiJing injection by UPLC-MS/MS, Chin. Tradit. Pat. Med. 39 (2017) 1183-1187
    L. Zuo, Z. Sun, Y. Hu, et al., Rapid determination of 30 bioactive constituents in XueBiJing injection using ultra high performance liquid chromatography-high resolution hybrid quadrupole-orbitrap mass spectrometry coupled with principal component analysis, J. Pharmaceut. Biomed. 137 (2017) 220-228
    Z. Sun, L. Zuo, T.-W. Sun, et al., Chemical profiling and quantification of XueBiJing injection, a systematic quality control strategy using UHPLC-Q exactive hybrid quadrupoleorbitrap high-resolution mass spectrometry, Sci. Rep. 7 (2017), 16921
    Z. Sun, L. Zhou, L.-H. Zuo, et al., Digital fingerprint of XueBiJing injections by UPLC and content determination of four phenolic acids, Chin. J. Hosp. Pharm. 33 (2017) 1060-1064
    D. Li, X.-X. Cao, W.-L. Pu, et al., Research on quality control method of XueBiJing injection, Mod. Chin. Med. 20 (2018) 1157-1160
    Z.-G. Huang, G. Cheng, H. Tang, et al., Studies on HPLC fingerprint of XueBiJing injection, Chin. J. Hosp. Pharm. 38 (2018) 2323-2327
    G.J. Kemp, Theoretical aspects of one-point calibration:causes and effects of some potential errors, and their dependence on concentration, Clin. Chem. 30 (1984) 1163-1167
    F.T. Peters, H.H. Maurer, Systematic comparison of bias and precision data obtained with multiple-point and one-point calibration in six validated multianalyte assays for quantification of drugs in human plasma, Anal. Chem. 79 (2007) 4967-4976
    N. Zhang, C. Cheng, O.E. Olaleye, et al., Pharmacokinetics-based identification of potential therapeutic phthalides from XueBiJing, a Chinese herbal injection used in sepsis management, Drug Metab. Dispos. 46 (2018) 823-834
    C. Cheng, J.-Z. Lin, L. Li, et al., Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats, Acta Pharmacol. Sin. 37 (2016) 530-544
    X. Li, C. Cheng, F. Wang, et al., Pharmacokinetics of catechols in human subjects intravenously receiving XueBiJing injection, an emerging antiseptic herbal medicine, Drug Metab. Pharmacokinet. 31 (2016) 95-98
    J. Li, O.E. Olaleye, X. Yua, et al., High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care, Acta Pharm. Sin. B 9 (2019) 1035-1049
    R. Bonfiglio, R.C. King, T.V. Olah, et al., The effects of sample preparation methods on the variability of the electrospray ionization response for model drug compounds, Rapid Commun. Mass Spectrom. 13 (1999) 1175-1185
    R. Zhang, Y. Wang, L. Tan, et al., Analysis of polysorbate 80 and its related compounds by RP-HPLC with ELSD and MS detection, J. Chromatogr. Sci. 50 (2012) 598-607
    M. Trötzmuller, A. Triebl, A. Ajsic, et al., Determination of the isotopic enrichment of 13C- and 2H-labeled tracers of glucose using high resolution mass spectrometry:application to dual- and triple-tracer studies, Anal. Chem. 89 (2017) 12252-12260
    Chinese Pharmacopoeia Commission, Pharmacopoeia of the People's Republic of China, Volume IV, China Medical Science Press, Beijing, 2020, pp. 480-483
    International Conference on Harmonization, Validation of Analytical Procedures:Text and Methodology Q2(R1), http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1_Guideline.pdf. (Accessed 28 June 2021)
    F. Chen, L. Li, F. Xu, et al., Systemic and cerebral exposure to and pharmacokinetics of flavonols and terpene lactones after dosing standardized Ginkgo biloba leaf extracts to rats via different routes of administration, Br. J. Pharmacol. 170 (2013) 440-457
    M. Li, F. Wang, Y. Huang, et al., Systemic exposure to and disposition of catechols derived from Salvia miltiorrhiza roots (Danshen) after intravenous dosing DanHong injection in human subjects, rats, and dogs, Drug Metab. Dispos. 43 (2015) 679-690
    C. Cheng, F. Du, K. Yu, et al., Pharmacokinetics and disposition of circulating iridoids and organic acids in rats intravenously receiving ReDuNing injection, Drug Metab. Dispos. 44 (2016) 1853-1858
    X.-W. Liu, J.-L. Yang, W. Niu, et al., Human pharmacokinetics of ginkgo terpene lactones and impact of carboxylation in blood on their platelet-activating factor antagonistic activity, Acta Pharm. Sin. 39 (2018) 1935-1946
    O.E. Olaleye, W. Niu, F.-F. Du, et al., Multiple circulating saponins from intravenous ShenMai inhibit OATP1Bs in vitro:potential joint precipitants of drug interactions, Acta Pharmacol. Sin. 40 (2018) 833-849
    S. Pintusophon, W. Niu, X.-N. Duan, et al., Intravenous formulation of Panax notoginseng root extract:human pharmacokinetics of ginsenosides and potential for perpetrating drug interactions, Acta Pharmacol. Sin. 40 (2019) 1351-1363
    X.-M. Chen, X.-W. Wang, J. Luo, et al., Pharmacokinetic studies of XueBiJing injection in rats, Chin. J. Pharm. Anal. 32 (2012) 744-748
    L. Zuo, Q. Zhong, Z. Wang, et al., Simultaneous determination and pharmacokinetic study of twelve bioactive compounds in rat plasma after intravenous administration of XueBiJing injection by UHPLC-Q-Orbitrap HRMS, J. Pharmaceut. Biomed. Anal. 146 (2017) 347-353
    H.-Z. Ouyang, J. He, Simultaneous determination of nine constituents of XueBiJing injection in rat plasma and their pharmacokinetics by LC-MS/MS, Zhongguo Zhong Yao Za Zhi 43 (2018) 3553-3561
    L. Zuo, Z. Sun, Z. Wang, et al., Tissue distribution profiles of multiple major bioactive components in rats after intravenous administration of XueBiJing injection by UHPLC-Q-Orbitrap HRMS, Biomed. Chromatogr. 33 (2019), e4400
    X. Xu, Y. Guo, J. Zhao, et al., Hydroxysafflor yellow A inhibits LPS-induced NLRP3 inflammasome activation via binding to Xanthine Oxidase in mouse RAW264.7 macrophages, Mediators Inflamm. 2016 (2016), 8172706
    C.-Y. Sun, C.-Q. Pei, B.-X. Zang, et al., The ability of hydroxysafflor yellow A to attenuate lipopolysaccharide-induced pulmonary inflammatory injury in mice, Phytother. Res. 24 (2010) 1788-1795
    Y. Sun, D.-P. Xu, Z. Qin, et al., Protective cerebrovascular effects of hydroxysafflor yellow A (HSYA) on ischemic stroke, Eur. J. Pharmacol. 818 (2018) 604-609
    D.B. Ji, M.C. Zhu, B. Zhu, et al., Hydroxysafflor yellow A enhances survival of vascular endothelial cells under hypoxia via upregulation of the HIF-1α-VEGF Pathway and Regulation of Bcl-2/Bax, J. Cardiovasc. Pharmacol. 52 (2008) 191-202
    J. Bai, J. Zhao, D. Cui, et al., Protective effect of hydroxysafflor yellow A against acute kidney injury via the TLR4/NF-κB signaling pathway, Sci. Rep. 8 (2018), 9173
    M. Jiang, M.-G. Zhou, Y.-Q. Han, et al., Identification of NF-κB inhibitors in XueBiJing injection for sepsis treatment based on bioactivity-integrated UPLC-Q/TOF, J. Ethnopharmacol. 147 (2013) 426-433
    W.-L. Jiang, X.-G. Chen, H.-B. Zhu, et al., Paeoniflorin inhibits systemic inflammation and improves survival in experimental sepsis, Basic Clin. Pharmacol. Toxicol. 105 (2009) 64-71
    Q.-S. Wang, T. Gao, Y.-L. Cui, et al., Comparative studies of paeoniflorin and albiflorin from Paeonia lactiflora on anti-inflammatory activities, Pharm. Biol. 52 (2014) 1189-1195
    X.-X. Wu, X.-L. Huang, R.-R. Chen, et al., Paeoniflorin prevents intestinal barrier disruption and inhibits Lipopolysaccharide (LPS)-induced inflammation in Caco-2 cell monolayers, Inflammation 42 (2019) 2215-2225
    B. Liu, J. Lin, L. Bai, et al., Paeoniflorin inhibits mesangial cell proliferation and inflammatory response in rats with mesangial proliferative glomerulonephritis through PI3K/AKT/GSK-3β pathway, Front. Pharmacol. 10 (2019), 978
    Y. Wang, J. Che, H. Zhao, et al., Paeoniflorin attenuates oxidized low-density lipoprotein-induced apoptosis and adhesion molecule expression by autophagy enhancement in human umbiblical vein endothelial cells, J. Cell. Biochem. 120 (2019) 9291-9299
    J. Wen, B. Xu, Y. Sun, et al., Paeoniflorin protects against intestinal ischemia/reperfusion by activating LKB1/AMPK and promoting autophagy, Pharmacol. Res. 146 (2019), 104308
    J. Ye, H. Duan, X. Yang, et al., Anti-thrombosis effect of paeoniflorin:evaluated in a photochemical reaction thrombosis model in vivo, Planta. Med. 67 (2001) 766-767
    M. Zhu, Y.-P. Tang, J.-A. Duan, et al., Roles of paeoniflorin and senkyunolide I in SiWu decoction on antiplatelet and anticoagulation activities, J. Sep. Sci. 33 (2010) 3335-3340
    L. Ji, X. Hou, W. Liu, et al., Paeoniflorin inhibits activation of the IRAK1-NF-κB signaling pathway in peritoneal macrophages from lupus-prone MRL/lpr mice, Microb. Pathog. 124 (2018) 223-229
    Y. Hu, M. Duan, S. Liang, et al., Senkyunolide I protects rat brain against focal cerebral ischemia-reperfusion injury by up-regulating p-Erk1/2, Nrf2/HO-1 and inhibiting caspase 3, Brain Res. 1605 (2015) 39-48
    E.O. Kim, K.J. Min, T.K. Kwon, et al., Anti-inflammatory activity of hydroxycinnamic acid derivatives isolated from corn bran in lipopolysaccharide-stimulated Raw 264.7 macrophages, Food Chem. Toxicol. 50 (2012) 1309-1316
    M. Bacanli, S. Aydin, G. Taner, The protective role of ferulic acid on sepsis-induced oxidative damage in Wistar albino rats, Environ. Toxicol. Pharmacol. 38 (2014) 774-782
    S. Shuai, G. Yue, Ferulic Acid, A potential antithrombotic drug, J. Lung Health Dis. 2 (2018) 25-28
    Y. Yin, F. Qi, Z. Song, et al., Ferulic acid combined with astragaloside IV protects against vascular endothelial dysfunction in diabetic rats, Biosci. Trends 8 (2014) 217-226
    J.H. Choi, J.K. Park, K.M. Kim, et al., In vitro and in vivo antithrombotic and cytotoxicity effects of ferulic acid, J. Biochem. Mol. Toxicol. 32 (2018), e22004
    J.-F. Xu, L. Yang, L.-A. Dong, Tanshinol upregulates the expression of aquaporin 5 in lung tissue of rats with sepsis, Oncol. Lett. 16 (2018) 3290-3296
    G.-R. Zhao, H.-M. Zhang, T.-X. Ye, et al., Characterization of the radical scavenging and antioxidant activities of danshensu and salvianolic acid B, Food Chem. Toxicol. 46 (2008) 73-81
    C. Chen, G. Cheng, X. Yang, et al., Tanshinol suppresses endothelial cells apoptosis in mice with atherosclerosis via lncRNA TUG1 up-regulating the expression of miR-26a, Am. J. Transl. Res. 8 (2016) 2981-2991
    S.W. Min, S.N. Ryu, D.H. Kim, Anti-inflammatory effects of black rice, cyanidin-3-O-β-D -glycoside, and its metabolites, cyanidin and protocatechuic acid, Int. Immunopharmacol. 10 (2010) 959-966
    X. Zhang, C. Li, J. Li, et al., Protective effects of protocatechuic acid on acute lung injury induced by lipopolysaccharide in mice via p38MAPK and NF-κB signal pathways, Int. Immunopharmacol. 26 (2015) 229-236
    J.-J. Yan, J.-S. Jung, Y.-J. Hong, et al., Protective effect of protocatechuic acid isopropyl ester against murine models of sepsis:inhibition of TNF-α and nitric oxide production and augmentation of IL-10, Biol. Pharm. Bull. 27 (2004) 2024-2027
    T.-H. Chou, H.-Y. Ding, R.-J. Lin, et al., Inhibition of melanogenesis and oxidation by protocatechuic acid from origanum wulgare (oregano), J. Nat. Prod. 73 (2010) 1767-1774
    R. Zheng, H. Wang, Z. Liu, et al., A real-world study on adverse drug reactions to XueBiJing injection:hospital intensive monitoring based on 93 hospitals (31,913 cases), Ann. Transl. Med. 7 (2019) 117
    B. Nair. Final report on the safety assessment of benzyl alcohol, benzoic acid, and sodium benzoate, Int. J. Toxicol. 20 (2001) 23-50
    M. Kaouadji, F.D. Pachtere, C. Pouget, et al., Three additional phthalide derivatives, an epoxymonomer and two dimers, from Ligusticum wallichii Rhizomes, J. Nat. Prod. 49 (1986) 872-877
    J.-L. Liu, Q.-J. Fan, S.-L. Zheng, et al., Quantitative determination of 5 active ingredients in different harvest periods of Ligusticum chuanxiong by HPLC, Zhongguo Zhong Yao Za Zhi 39 (2014) 1650-1655
    Y. Cao, Y.-F. Chai, Y. Deng, et al., Chinese guidelines for emergency management of sepsis and septic shock 2018, J. Clin. Emerg. 19 (2018) 567-588
    G.-Z. Zhao, R.-B. Chen, B. Li, et al., Clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for sepsis, Ann. Transl. Med. 7 (2019), 122
    Chinese Society of Emergency Medicine, Editorial Board of Chinese Critical Care Medicine, Expert Group of Chinese Emergency Medicine Expert Consensus on Diagnosis and Treatment of Sepsis Complicated with Disseminated Intravascular Coagulation, et al., Chinese emergency medicine expert consensus on diagnosis and treatment of sepsis complicated with disseminated intravascular coagulation, Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 29 (2017) 577-580
    D.C. Angus and T. van der Poll, Severe sepsis and septic shock, N. Engl. J. Med. 369 (2013) 840-851
    T. van der Poll, F.L. van de Veerdonk, B.P. Scicluna, et al., The immunopathology of sepsis and potential therapeutic targets, Nat. Rev. Immunol. 17 (2017) 407-420
    Q. Yin, C. Li, Treatment effects of XueBiJing injection in severe septic patients with disseminated intravascular coagulation, Evid. Based Complement. Alternat. Med. 2014 (2014), 949254
    X. Chen, Y. Feng, X. Shen, et al., Anti-sepsis protection of XueBiJing injection is mediated by differential regulation of pro- and anti-inflammatory Th17 and T regulatory cells in a murine model of polymicrobial sepsis, J. Ethnopharmacol. 211 (2018) 358-365
    L. Wang, Z. Liu, Z. Dong, et al., Effects of XueBiJing injection on microcirculation in septic shock, J. Surg. Res. 202 (2016) 147-154
    T.-H. Dong, G.-P. Zhang, K. Dong, et al., Research progress on mechanism of action of XueBiJing injection in the treatment of sepsis, Chin. J. Tradit. Chin. Med. West. Med. Crit. Care 23 (2016) 554-557
    Q. Wang, X. Wu, X. Tong, et al., XueBiJing ameliorates sepsis-induced lung injury by downregulating HMGB1 and RAGE expressions in mice, Evid. Based Complement. Alternat. Med. 2015 (2015), 860259
    L. Zuo, L. Zhou, T. Xu, et al., Antiseptic activity of ethnomedicinal XueBiJing revealed by the metabolomics analysis using UHPLC-Q-Orbitrap HRMS, Front. Pharmacol. 9 (2018), 300
    T. Xu, L. Zhou, Y. Shi, et al., Metabolomics approach in lung tissue of septic rats and the interventional effects of XueBiJing injection using UHPLC-Q-Orbitrap-HRMS, J. Biochem. 164 (2018) 427-435
    L. Li, Y. Zhao, F. Du, et al., Intestinal absorption and presystemic elimination of various chemical constituents present in GBE50 extract, a standardized extract of Ginkgo biloba leaves, Curr. Drug Metab. 13 (2012) 494-509
    Z. Hu, J. Yang, C. Cheng, et al., Combinatorial metabolism notably affects human systemic exposure to ginsenosides from orally administered extract of Panax notoginseng roots (Sanqi), Drug Metab. Dispos. 41 (2013) 1457-1469
    X.-F. Lan, O.E. Olaleye, J.-L. Lu, et al., Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule, Acta Pharmocol. Sin. 42 (2021) 2155-2172
    B.-L. Zhang, C.-H. Chen, Modernization of Chinese medicine for twenty years (1996-2015), Shanghai Scientific & Technical Publishers, Shanghai, 2016
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)

    Article Metrics

    Article views (262) PDF downloads(20) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return