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Simultaneous determination of two iridoid glycosides, two anthraquinones and four flavonoid glycosides of Zhi-Zi-Da-Huang decoction in rat plasma by UFLC-MS/MS: application to a comparative pharmacokinetic study in normal and cholestatic liver injury rats.

Abstract

A selective, sensitive and reliable ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed for the simultaneous determination of two iridoid glycosides (geniposide and genipin gentiobioside), two anthraquinones (rhein and emodin) and four flavonoid glycosides (isonaringin, naringin, hesperidin and neohesperidin), the major active ingredients of Zhi-Zi-Da-Huang decoction (ZZDHD), in rat plasma using paeoniflorin as internal standard (IS). After liquid-liquid extraction with ethyl acetate-isopropanol (1:1, v/v), separation was achieved on a Shim-pack XR-ODS C18 column (75 mm×3.0 mm, 2.2 μm) using gradient elution with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.4 mL/min. Detection was performed on 4000 QTRAP mass spectrometry equipped with turbo ion spray source in the negative ionization and multiple reaction monitoring (MRM) mode. The intra- and inter-day precisions (as relative standard deviation) were less than 11.4%, and accuracy (as relative error) was within ± 10.0%. The lower limits of quantification (LLOQ) were 4.0, 0.5, 2.0, 0.1, 1.0, 2.0, 1.0, 2.0 ng/mL for geniposide, genipin gentiobioside, rhein, emodin, isonaringin, naringin, hesperidin and neohesperidin, respectively. The extraction recoveries of the analytes and IS from rat plasma were all more than 86.0%. The method was fully validated and applied to compare the pharmacokinetic profiles of the analytes in normal and cholestatic liver injury (CLI) rats after oral administration of ZZDHD. Results showed that there were remarkable differences in pharmacokinetic properties of the analytes between normal and CLI group.

Authors+Show Affiliations

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China; School of Pharmacy, Jilin Medical College, 5 Jilin Street, Fengman District, Jilin 132013, China.School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China; School of Pharmacy, Jilin Medical College, 5 Jilin Street, Fengman District, Jilin 132013, China.School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: yinran_syphu@163.com.School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: houxiaohong@syphu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24793084

Citation

Zhu, Heyun, et al. "Simultaneous Determination of Two Iridoid Glycosides, Two Anthraquinones and Four Flavonoid Glycosides of Zhi-Zi-Da-Huang Decoction in Rat Plasma By UFLC-MS/MS: Application to a Comparative Pharmacokinetic Study in Normal and Cholestatic Liver Injury Rats." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 960, 2014, pp. 116-25.
Zhu H, Bi K, Han F, et al. Simultaneous determination of two iridoid glycosides, two anthraquinones and four flavonoid glycosides of Zhi-Zi-Da-Huang decoction in rat plasma by UFLC-MS/MS: application to a comparative pharmacokinetic study in normal and cholestatic liver injury rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;960:116-25.
Zhu, H., Bi, K., Han, F., Guan, J., Tang, Z., Chen, K., Zhao, L., Li, Q., Yin, R., & Hou, X. (2014). Simultaneous determination of two iridoid glycosides, two anthraquinones and four flavonoid glycosides of Zhi-Zi-Da-Huang decoction in rat plasma by UFLC-MS/MS: application to a comparative pharmacokinetic study in normal and cholestatic liver injury rats. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 960, 116-25. https://doi.org/10.1016/j.jchromb.2014.04.031
Zhu H, et al. Simultaneous Determination of Two Iridoid Glycosides, Two Anthraquinones and Four Flavonoid Glycosides of Zhi-Zi-Da-Huang Decoction in Rat Plasma By UFLC-MS/MS: Application to a Comparative Pharmacokinetic Study in Normal and Cholestatic Liver Injury Rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jun 1;960:116-25. PubMed PMID: 24793084.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simultaneous determination of two iridoid glycosides, two anthraquinones and four flavonoid glycosides of Zhi-Zi-Da-Huang decoction in rat plasma by UFLC-MS/MS: application to a comparative pharmacokinetic study in normal and cholestatic liver injury rats. AU - Zhu,Heyun, AU - Bi,Kaishun, AU - Han,Fei, AU - Guan,Jiao, AU - Tang,Zheng, AU - Chen,Kelin, AU - Zhao,Longshan, AU - Li,Qing, AU - Yin,Ran, AU - Hou,Xiaohong, Y1 - 2014/04/24/ PY - 2014/01/09/received PY - 2014/04/10/revised PY - 2014/04/13/accepted PY - 2014/5/6/entrez PY - 2014/5/6/pubmed PY - 2015/1/13/medline KW - Cholestatic liver injury KW - Pharmacokinetics KW - Rat plasma KW - UFLC-MS/MS KW - Zhi-Zi-Da-Huang decoction SP - 116 EP - 25 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J Chromatogr B Analyt Technol Biomed Life Sci VL - 960 N2 - A selective, sensitive and reliable ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed for the simultaneous determination of two iridoid glycosides (geniposide and genipin gentiobioside), two anthraquinones (rhein and emodin) and four flavonoid glycosides (isonaringin, naringin, hesperidin and neohesperidin), the major active ingredients of Zhi-Zi-Da-Huang decoction (ZZDHD), in rat plasma using paeoniflorin as internal standard (IS). After liquid-liquid extraction with ethyl acetate-isopropanol (1:1, v/v), separation was achieved on a Shim-pack XR-ODS C18 column (75 mm×3.0 mm, 2.2 μm) using gradient elution with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.4 mL/min. Detection was performed on 4000 QTRAP mass spectrometry equipped with turbo ion spray source in the negative ionization and multiple reaction monitoring (MRM) mode. The intra- and inter-day precisions (as relative standard deviation) were less than 11.4%, and accuracy (as relative error) was within ± 10.0%. The lower limits of quantification (LLOQ) were 4.0, 0.5, 2.0, 0.1, 1.0, 2.0, 1.0, 2.0 ng/mL for geniposide, genipin gentiobioside, rhein, emodin, isonaringin, naringin, hesperidin and neohesperidin, respectively. The extraction recoveries of the analytes and IS from rat plasma were all more than 86.0%. The method was fully validated and applied to compare the pharmacokinetic profiles of the analytes in normal and cholestatic liver injury (CLI) rats after oral administration of ZZDHD. Results showed that there were remarkable differences in pharmacokinetic properties of the analytes between normal and CLI group. SN - 1873-376X UR - https://www.unboundmedicine.com/medline/citation/24793084/Simultaneous_determination_of_two_iridoid_glycosides_two_anthraquinones_and_four_flavonoid_glycosides_of_Zhi_Zi_Da_Huang_decoction_in_rat_plasma_by_UFLC_MS/MS:_application_to_a_comparative_pharmacokinetic_study_in_normal_and_cholestatic_liver_injury_rats_ DB - PRIME DP - Unbound Medicine ER -