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Pharmacokinetics and tissue distribution of five major triterpenoids after oral administration of Rhizoma Alismatis extract to rats using ultra high-performance liquid chromatography-tandem mass spectrometry.
J Pharm Biomed Anal 2017; 146:314-323JP

Abstract

Rhizoma Alismatis (RA) was wildly used for treatment of dysuria, pyelonephritis, hyperlipidemia, enteritis diarrhea, diabetes, inflammation, and cancer. Triterpenoids are the major active components of RA, and its extract is mainly composed of alisol A (ALA), alisol B (ALB), alisol C 23-acetate (ALC-23A), alisol A 24-acetate (ALA-24A), and alisol B 23-acetate (ALB-23A). In this study, a simple, reliable, and sensitive ultra high-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-MS/MS) method was created and validated for the quantification of the five major triterpenoids in rat plasma and various tissues biosamples (including intestine, stomach, liver, kidney, fat, muscle, brain, heart, lung, spleen, and testes). The plasma and tissues biosamples were pretreated by direct precipitation deproteinization method with acetonitrile. 17α-Hydroxyprogesterone was used as internal standard (IS). The chromatography was performed on a Phenomenex C8 column (30×2.00mm, 1.8μm) at room temperature with gradient elution. Compounds were quantified by selected multi-reactions monitoring (SRM) scanning with positive electric spray ionization mode. The linearity of detection for each triterpene was respectively from 1 to 1000ng/mL for ALC-23A and ALA, from 4 to 4000ng/mL for ALA-24A, from 10 to 10,000ng/mL for ALB, and from 2 to 2000ng/mL for ALB-23B (r>0.99) with low quantification limits of 1-10ng/mL for all analytes. All of the other validation parameters were also in an acceptable range. The validated UHPLC-MS/MS method subsequently applied for the pharmacokinetic and tissue distribution studies of RA extract. After orally given 100mg/kg of RA extract, ALA was the most exposed component, followed by ALB and ALA-24A. Whereas significant gender difference was observed for ALB, ALA, and ALA-24A between female and male rats. The AUC(0-∞) of ALA, ALB, and ALA-24A in female rats were approximately 2-5 fold larger than that in male rats. These triterpenoids also displayed approximately 1.5-2 times longer half-life (t1/2) in female rats. Appearant Km, Vmax and Clint of ALA, ALB, and ALA-24A were calculated by substrate depletion approach, rat P450 CYP3A2 plays an important role in the metabolism of ALA, ALB, and ALA-24A, which is an important factor leading to the different exprosures of ALA, ALB, and ALA-24A between the male rats and the female rats. Furthermore, results from tissue distribution in male rats showed that the main tissue depots of five triterpenoids were the stomach/intestine, followed by the liver, brain, and fat. However, ALA was still measured in the kidney after a long elimination time. ALB and ALB-23B exhibited lower elimination rate in the testis. These results provide a fundamental support for further pharmacological development and clinical safety application of RA.

Authors+Show Affiliations

College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.Department of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan; School of Pharmacy, China Medical University, Taichung 40402, Taiwan; Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan.College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. Electronic address: hmq1115@126.com.College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. Electronic address: wushuishengwss@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28910706

Citation

Xu, Wen, et al. "Pharmacokinetics and Tissue Distribution of Five Major Triterpenoids After Oral Administration of Rhizoma Alismatis Extract to Rats Using Ultra High-performance Liquid Chromatography-tandem Mass Spectrometry." Journal of Pharmaceutical and Biomedical Analysis, vol. 146, 2017, pp. 314-323.
Xu W, Li X, Lin N, et al. Pharmacokinetics and tissue distribution of five major triterpenoids after oral administration of Rhizoma Alismatis extract to rats using ultra high-performance liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2017;146:314-323.
Xu, W., Li, X., Lin, N., Zhang, X., Huang, X., Wu, T., ... Wu, S. (2017). Pharmacokinetics and tissue distribution of five major triterpenoids after oral administration of Rhizoma Alismatis extract to rats using ultra high-performance liquid chromatography-tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 146, pp. 314-323. doi:10.1016/j.jpba.2017.09.009.
Xu W, et al. Pharmacokinetics and Tissue Distribution of Five Major Triterpenoids After Oral Administration of Rhizoma Alismatis Extract to Rats Using Ultra High-performance Liquid Chromatography-tandem Mass Spectrometry. J Pharm Biomed Anal. 2017 Nov 30;146:314-323. PubMed PMID: 28910706.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics and tissue distribution of five major triterpenoids after oral administration of Rhizoma Alismatis extract to rats using ultra high-performance liquid chromatography-tandem mass spectrometry. AU - Xu,Wen, AU - Li,Xiaoyan, AU - Lin,Na, AU - Zhang,Xue, AU - Huang,Xiaoqiang, AU - Wu,Tingting, AU - Tai,Yanni, AU - Chen,Shuyun, AU - Wu,Chieh-Hsi, AU - Huang,Mingqing, AU - Wu,Shuisheng, Y1 - 2017/09/06/ PY - 2017/05/05/received PY - 2017/09/02/revised PY - 2017/09/05/accepted PY - 2017/9/15/pubmed PY - 2018/5/31/medline PY - 2017/9/15/entrez KW - Pharmacokinetics KW - Rhizoma Alismatis KW - Tissue distribution KW - Triterpenoids KW - UHPLC–MS/MS SP - 314 EP - 323 JF - Journal of pharmaceutical and biomedical analysis JO - J Pharm Biomed Anal VL - 146 N2 - Rhizoma Alismatis (RA) was wildly used for treatment of dysuria, pyelonephritis, hyperlipidemia, enteritis diarrhea, diabetes, inflammation, and cancer. Triterpenoids are the major active components of RA, and its extract is mainly composed of alisol A (ALA), alisol B (ALB), alisol C 23-acetate (ALC-23A), alisol A 24-acetate (ALA-24A), and alisol B 23-acetate (ALB-23A). In this study, a simple, reliable, and sensitive ultra high-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-MS/MS) method was created and validated for the quantification of the five major triterpenoids in rat plasma and various tissues biosamples (including intestine, stomach, liver, kidney, fat, muscle, brain, heart, lung, spleen, and testes). The plasma and tissues biosamples were pretreated by direct precipitation deproteinization method with acetonitrile. 17α-Hydroxyprogesterone was used as internal standard (IS). The chromatography was performed on a Phenomenex C8 column (30×2.00mm, 1.8μm) at room temperature with gradient elution. Compounds were quantified by selected multi-reactions monitoring (SRM) scanning with positive electric spray ionization mode. The linearity of detection for each triterpene was respectively from 1 to 1000ng/mL for ALC-23A and ALA, from 4 to 4000ng/mL for ALA-24A, from 10 to 10,000ng/mL for ALB, and from 2 to 2000ng/mL for ALB-23B (r>0.99) with low quantification limits of 1-10ng/mL for all analytes. All of the other validation parameters were also in an acceptable range. The validated UHPLC-MS/MS method subsequently applied for the pharmacokinetic and tissue distribution studies of RA extract. After orally given 100mg/kg of RA extract, ALA was the most exposed component, followed by ALB and ALA-24A. Whereas significant gender difference was observed for ALB, ALA, and ALA-24A between female and male rats. The AUC(0-∞) of ALA, ALB, and ALA-24A in female rats were approximately 2-5 fold larger than that in male rats. These triterpenoids also displayed approximately 1.5-2 times longer half-life (t1/2) in female rats. Appearant Km, Vmax and Clint of ALA, ALB, and ALA-24A were calculated by substrate depletion approach, rat P450 CYP3A2 plays an important role in the metabolism of ALA, ALB, and ALA-24A, which is an important factor leading to the different exprosures of ALA, ALB, and ALA-24A between the male rats and the female rats. Furthermore, results from tissue distribution in male rats showed that the main tissue depots of five triterpenoids were the stomach/intestine, followed by the liver, brain, and fat. However, ALA was still measured in the kidney after a long elimination time. ALB and ALB-23B exhibited lower elimination rate in the testis. These results provide a fundamental support for further pharmacological development and clinical safety application of RA. SN - 1873-264X UR - https://www.unboundmedicine.com/medline/citation/28910706/Pharmacokinetics_and_tissue_distribution_of_five_major_triterpenoids_after_oral_administration_of_Rhizoma_Alismatis_extract_to_rats_using_ultra_high_performance_liquid_chromatography_tandem_mass_spectrometry_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0731-7085(17)31098-1 DB - PRIME DP - Unbound Medicine ER -