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Simultaneous determination of ten compounds in rat plasma by UPLC-MS/MS: Application in the pharmacokinetic study of Ma-Zi-Ren-Wan.

Abstract

Ma-Zi-Ren-Wan (MZRW) is a classic Chinese formula which has been used to treat human constipation in China for over 2000 years. In order to make good and rational use of this formula in the future, this paper presents the first attempt to track the pharmacokinetic features of MZRW in rat using rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Ten chemical components of MZRW, namely, rhein, emodin, aloe emodin, hesperidin, naringin, amygdalin, albiflorin, paeoniflorin, magnolol and honokiol, were simultaneously determined in rat plasma after a single oral administration (10g/kg body weight) of MZRW to rats. Geniposide and liquiritin were used as internal standards. The separation was performed on a Waters ACQUITY BEH C18 column (100mm×2.1mm, 1.7μm). The detection was conducted by multiple-reaction monitoring (MRM) in negative ionization mode. Two highest abundant MRM transitions without interference were optimized for each analyte. This method was well validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves had good linearity (r(2)>0.995) over the concentration range from 3.9 to 125.0ng/mL for emodin, 3.9-500.0ng/mL for amygdalin, 2.0-4000.0ng/mL for naringin and hesperidin, 3.9-2000.0ng/mL for magnolol, 7.8-2000.0ng/mL for rhein and 3.9-4000.0ng/mL for albiflorin, paeoniflorin, aloe emodin and honokiol. The intra-day and inter-day precision (relative standard deviation) was within 15%, the accuracy (relative error) ranged from -13.6% to 15.1%, and the lower limit of quantification in plasma ranged between 2.0ng/mL and 7.8ng/mL. Extraction recovery, matrix effect and stability were satisfactory. The validated method was successfully applied to a pharmacokinetic study of these ten compounds after oral administration of MZRW to rats. The pharmacokinetic parameters of each compound can facilitate clinical studies in the future.

Authors+Show Affiliations

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China; Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; Guangzhou Research Institute of Snake Venom, Guangzhou Medical University, Guangzhou 510000, China.Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; First School of Clinic Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510000, China.School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China.School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China. Electronic address: xuhongxi88@gmail.com.Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. Electronic address: bzxiang@hkbu.edu.hk.

Pub Type(s)

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

Language

eng

PubMed ID

26231677

Citation

Hu, Dong-Dong, et al. "Simultaneous Determination of Ten Compounds in Rat Plasma By UPLC-MS/MS: Application in the Pharmacokinetic Study of Ma-Zi-Ren-Wan." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 1000, 2015, pp. 136-46.
Hu DD, Han QB, Zhong LL, et al. 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;1000:136-46.
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. (2015). Simultaneous determination of ten compounds in rat plasma by UPLC-MS/MS: Application in the pharmacokinetic study of Ma-Zi-Ren-Wan. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 1000, 136-46. https://doi.org/10.1016/j.jchromb.2015.07.003
Hu DD, et al. 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 Sep 1;1000:136-46. PubMed PMID: 26231677.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simultaneous determination of ten compounds in rat plasma by UPLC-MS/MS: Application in the pharmacokinetic study of Ma-Zi-Ren-Wan. AU - Hu,Dong-Dong, AU - Han,Quan-Bin, AU - Zhong,Linda Li-Dan, AU - Li,Yan-Hong, AU - Lin,Cheng-Yuan, AU - Ho,Hing-Man, AU - Zhang,Man, AU - Lin,Shu-Hai, AU - Zhao,Ling, AU - Huang,Tao, AU - Mi,Hong, AU - Tan,Hong-Sheng, AU - Xu,Hong-Xi, AU - Bian,Zhao-Xiang, Y1 - 2015/07/14/ PY - 2015/02/03/received PY - 2015/06/04/revised PY - 2015/07/03/accepted PY - 2015/8/2/entrez PY - 2015/8/2/pubmed PY - 2016/2/4/medline KW - Active ingredient KW - Ma-Zi-Ren-Wan KW - Pharmacokinetics KW - Rat plasma KW - UPLC-MS/MS SP - 136 EP - 46 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. VL - 1000 N2 - Ma-Zi-Ren-Wan (MZRW) is a classic Chinese formula which has been used to treat human constipation in China for over 2000 years. In order to make good and rational use of this formula in the future, this paper presents the first attempt to track the pharmacokinetic features of MZRW in rat using rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Ten chemical components of MZRW, namely, rhein, emodin, aloe emodin, hesperidin, naringin, amygdalin, albiflorin, paeoniflorin, magnolol and honokiol, were simultaneously determined in rat plasma after a single oral administration (10g/kg body weight) of MZRW to rats. Geniposide and liquiritin were used as internal standards. The separation was performed on a Waters ACQUITY BEH C18 column (100mm×2.1mm, 1.7μm). The detection was conducted by multiple-reaction monitoring (MRM) in negative ionization mode. Two highest abundant MRM transitions without interference were optimized for each analyte. This method was well validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves had good linearity (r(2)>0.995) over the concentration range from 3.9 to 125.0ng/mL for emodin, 3.9-500.0ng/mL for amygdalin, 2.0-4000.0ng/mL for naringin and hesperidin, 3.9-2000.0ng/mL for magnolol, 7.8-2000.0ng/mL for rhein and 3.9-4000.0ng/mL for albiflorin, paeoniflorin, aloe emodin and honokiol. The intra-day and inter-day precision (relative standard deviation) was within 15%, the accuracy (relative error) ranged from -13.6% to 15.1%, and the lower limit of quantification in plasma ranged between 2.0ng/mL and 7.8ng/mL. Extraction recovery, matrix effect and stability were satisfactory. The validated method was successfully applied to a pharmacokinetic study of these ten compounds after oral administration of MZRW to rats. The pharmacokinetic parameters of each compound can facilitate clinical studies in the future. SN - 1873-376X UR - https://www.unboundmedicine.com/medline/citation/26231677/Simultaneous_determination_of_ten_compounds_in_rat_plasma_by_UPLC_MS/MS:_Application_in_the_pharmacokinetic_study_of_Ma_Zi_Ren_Wan_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1570-0232(15)30070-2 DB - PRIME DP - Unbound Medicine ER -