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Metabolite profiling analysis of plasma, urine, and feces of rats after oral administration of Flos Chrysanthemi Indici preparation through UHPLC-Q-Exactive-MS combined with pharmacokinetic study of markers by UHPLC-QQQ-MS/MS

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Abstract

Zhenju Antihypertensive Tablet is one of the Flos Chrysanthemi Indici preparations (FCIP) with antihypertensive effect. In order to investigate its process in vivo, a method using ultra-high performance liquid chromatography coupled with quadruple Exactive mass spectrometry (UHPLC-Q-Exactive-MS) was established for comprehensive analysis of the absorbed active component and metabolites in rat plasma, urine, and feces after the oral administration of FCIP. As a result, a total of 61 FCIP-related xenobiotics were identified, including 35 in plasma (25 prototypes, 10 metabolites), 40 in urine (23 prototypes, 17 metabolites), and 25 in feces (12 prototypes, 13 metabolites). The metabolism reactions included phase I reactions (such as oxidation, methylation, and reduction) and phase II reactions (such as sulfate conjugation and glucuronide conjugation). Meanwhile, a verified and optimized ultra-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method was developed for the simultaneous investigation of the pharmacokinetic profiles of four markers in FCIP. The results showed that all of the four components had good oral absorption effect. This study simultaneously investigated the comprehensive metabolic profiling of FCIP in rat plasma, urine, and feces after the oral administration as well as the four components pharmacokinetic behavior. The results can provide the therapeutic material basis for FCIP.

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Abbreviations

AUC:

Area under curves

Cmax :

Maximum plasma drug concentration

CA:

Chlorogenic acid

CV:

Coefficient of variation

EIC:

Extracted ion chromatogram

ESI:

Electrospray ionization source

FCI:

Flos Chrysanthemi Indici

FCIP:

Flos Chrysanthemi Indici Preparation

HCTZ:

Hydrochlorothiazide

HQC:

High concentration quality control samples

IS:

Internal standard

LLOQ:

Lower limit of quantification

LOD:

Limit of detection

LQC:

Low concentration quality control samples

LR:

Linarin

MQC:

Medium concentration quality control samples

RT:

Rutin

T1/2 :

Elimination half-life

Tmax :

Peak time

TCM:

Traditional Chinese medicine

References

  1. Li HY, Cao JL, Wu X, Deng Y, Wang YT. Multiple fingerprint profiling for quality evaluation of polysaccharides and related biological activity analysis of Chinese patent drugs: Zishen Yutai Pills as a case study. J Ethnopharmacol. 2020;260:113045.

    Article  CAS  Google Scholar 

  2. Zhang L, Wang C, Wu J, Wang T, Zhong Q, Du Y, et al. Metabolic profiling of mice plasma, bile, urine and feces after oral administration of two licorice flavonones. J Ethnopharmacol. 2020;257:112892.

    Article  CAS  Google Scholar 

  3. Tang X, Zeng J, Dai Z, Chen M, Ye M, Yao Z, et al. Identification and characterization of chemical constituents in Qi-Lin pills and their metabolites in rat bio-samples after oral administration using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry. J Pharm Biomed Anal. 2020;188:113402.

    Article  CAS  Google Scholar 

  4. Gao WY, Si N, Li ML, Gu XR, Zhang Y, Zhou YY, et al. The integrated study on the chemical profiling and in vivo course to explore the bioactive constituents and potential targets of Chinese classical formula Qingxin Lianzi Yin Decoction by UHPLC-MS and network pharmacology approaches. J Ethnopharmacol. 2021;272:113917.

    Article  CAS  Google Scholar 

  5. Wan MQ, Liu XY, Gao H, Wang TX, Zhang YF, Jia LY, et al. Systematic analysis of the metabolites of Angelicae Pubescentis Radix by UPLC-Q-TOF-MS combined with metabonomics approaches after oral administration to rats. J Pharm Biomed Anal. 2020;188:113445.

    Article  CAS  Google Scholar 

  6. Lin QY, Pu HL, Guan HD, Ma C, Zhang YP, Ding WZ, et al. Rapid identification and pharmacokinetic studies of multiple active alkaloids in rat plasma through UPLC-Q-TOF-MS and UPLC-MS/MS after the oral administration of Zanthoxylum nitidum extract. J Pharm Biomed Anal. 2020;186:113232.

    Article  CAS  Google Scholar 

  7. Theuretzbacher U, Barbee L, Connolly K, Drusano G, Fernandes P, Hook E, et al. Pharmacokinetic/pharmacodynamic considerations for new and current therapeutic drugs for uncomplicated gonorrhoea—challenges and opportunities. Clin Microbiol Infect. 2020;26(12):1630–5.

    Article  CAS  Google Scholar 

  8. Mohamadi N, Sharififar F, Ansari M, Pournamdari M, Rezaei M, Hassanabadi N. Pharmacokinetic profile of diosgenin and trigonelline following intravenous and oral administration of fenugreek seed extract and pure compound in rabbit. J Asian Nat Prod Res. 2020;23(5):466–77.

    Article  Google Scholar 

  9. Shen S, Sha Y, Deng C, Zhang X, Fu D, Chen J. Quality assessment of Flos Chrysanthemi Indici from different growing areas in China by solid-phase microextraction-gas chromatography-mass spectrometry. J Chromatogr A. 2004;1047(2):281–7.

    Article  CAS  Google Scholar 

  10. Li X, Hu Q, Jiang S, Li F, Lin J, Han L, et al. Flos Chrysanthemi Indici protects against hydroxyl-induced damages to DNA and MSCs via antioxidant mechanism. J Saudi Chem Soc. 2015;19(4):454–60.

    Article  Google Scholar 

  11. Wang J, Dong C, Liang L, Xue P, Tu P. Chemical constituents from flowers of Chrysanthemum indicum. China J Chin Materia Med. 2010;35(6):718–21.

    CAS  Google Scholar 

  12. Xu XY, Tang YW, Huang DJ, Zhang GM. Establishment of the Fingerprint of Leishi Brand Zhenju Jiangya Tablet by HPLC. Mod Chin Med. 2011;013(011):39–42.

    CAS  Google Scholar 

  13. Zheng Y. Effect of Chinese and Western medicine compound Zhenju antihypertensive tablet on hypertension. Electron J Clin Med Lit. 2020;7(07):20.

    Google Scholar 

  14. Tian D, Yang Y, Yu M, Han Z, Wei M, Zhang H, et al. Anti-inflammatory chemical constituents of Flos Chrysanthemi Indici determined by UPLC-MS/MS integrated with network pharmacology. Food Funct. 2020;11(7):6340–51.

    Article  CAS  Google Scholar 

  15. Dai TT, Sun GX. The analysis of active compounds in Flos Chrysanthemi Indici by UHPLC Q exactive HF hybrid quadrupole-orbitrap MS and comprehensive quality assessment of its preparation. Food Funct. 2021;12(4):1769–82.

    Article  CAS  Google Scholar 

  16. Liu YT, Li XQ, Li AP, Li K, Qin XM. UHPLC Q-Exactive MS-based spleen metabolomics and lipidomics to explore the effect mechanisms of Danggui Buxue Decoction in anemia mice. J Pharm Biomed Anal. 2020;185:113234.

    Article  CAS  Google Scholar 

  17. Li J, Hua JJ, Yuan HB, Deng YL, Zhou QH, Yang YQ, et al. Investigation on green tea lipids and their metabolic variations during manufacturing by nontargeted lipidomics. Food Chem. 2021;339:128114.

    Article  CAS  Google Scholar 

  18. Chen ZY, Wang MM, Yang YY, Du X, Zhang ZJ. Qualitative and quantitative analysis of Porana sinensis Hemsl by UHPLC-Q-Exactive MS, TLC autographic method and DART-MS. Phytochem Anal Pca. 2018;30(3):311–9.

    Article  Google Scholar 

  19. Wang CJ, Ying X, Xiang Z, Zhou H, Liu L. Simultaneous determination of thirteen major active compounds in Guanjiekang preparation by UHPLC-QQQ-MS/MS. J Pharm Biomed Anal. 2016;118:315–21.

    Article  CAS  Google Scholar 

  20. Zhao XJ, Guo PM, Pang WH, Zhang YH, Zhao QY, Jiao BN, et al. A rapid UHPLC-QqQ-MS/MS method for the simultaneous qualitation and quantitation of coumarins, furocoumarins, flavonoids, phenolic acids in pummelo fruits. Food Chem. 2020;325:126835.

    Article  CAS  Google Scholar 

  21. Dominguez-Perles R, Medina S, Moreno DA, Garcia-Viguera C, Ferreres F, Gil-Izquierdo A. A new ultra-rapid UHPLC/MS/MS method for assessing glucoraphanin and sulforaphane bioavailability in human urine. Food Chem. 2014;143:132–8.

    Article  CAS  Google Scholar 

  22. Domon B, Costello CE. A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates. Glycoconj J. 1988;5(4):397–409.

    Article  CAS  Google Scholar 

  23. Cuyckens F, Claeys M. Mass spectrometry in the structural analysis of flavonoids. J Mass Spectrom. 2004;39(1):1–15.

    Article  CAS  Google Scholar 

  24. Dubey R, Ghosh M. Simultaneous determination and pharmacokinetic study of losartan, losartan carboxylic acid, ramipril, ramiprilat, and hydrochlorothiazide in rat plasma by a liquid chromatography/tandem mass spectrometry method. Sci Pharm. 2014;83(1):107.

    Article  Google Scholar 

  25. Li Y, Guang CX, Zhao N, Feng XC, Qiu F. LC–MS/MS method for simultaneous determination of linarin and its metabolites in rat plasma and liver tissue samples: application to pharmacokinetic and liver tissue distribution study after oral administration of linarin. Molecules. 2019;24(18):3342.

    Article  CAS  Google Scholar 

  26. Liu X, Tang D, Yin X, Gao Y, Wei Y, Chen Y. Pharmacokinetic study of rutin in normal and diabetic nephropathy rats. Acta Academiae Medicinae Xuzhou. 2009;29(11):708–12.

    CAS  Google Scholar 

  27. Yin Y, Sun Y. Pharmacokinetics research of chlorogenic acid and chlorogenic acid monomer in the Yinruikang capsule. Clin J Chin Med. 2019;11(35):1–6.

    CAS  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (Nos. 90612002 and 81573586).

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Authors and Affiliations

  1. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110032, Liaoning, China

    Tingting Dai & Guoxiang Sun

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  1. Tingting Dai
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Contributions

Tingting Dai: methodology, validation, formal analysis, investigation, data curation, visualization, writing — original draft, writing — review and editing. Guoxiang Sun: conceptualization, software, supervision, writing — review and editing, project administration, funding acquisition.

Corresponding author

Correspondence to Guoxiang Sun.

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All the animal experiments were carried out according to the Guideline for Shenyang Pharmaceutical University Animal Experimentation with permission by institutional Animal Ethics Committee.

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The authors declare no competing interests.

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Dai, T., Sun, G. Metabolite profiling analysis of plasma, urine, and feces of rats after oral administration of Flos Chrysanthemi Indici preparation through UHPLC-Q-Exactive-MS combined with pharmacokinetic study of markers by UHPLC-QQQ-MS/MS. Anal Bioanal Chem 414, 3927–3943 (2022). https://doi.org/10.1007/s00216-022-04037-z

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  • DOI: https://doi.org/10.1007/s00216-022-04037-z

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