TY - JOUR
T1 - Biopharmaceutical and pharmacokinetic characterization of matrine as determined by a sensitive and robust UPLC-MS/MS method
AU - Yang, Zhen
AU - Gao, Song
AU - Yin, Taijun
AU - Kulkarni, Kaustubh H.
AU - Teng, Yang
AU - You, Ming
AU - Hu, Ming
N1 - Funding Information:
The work was supported by NIH AT005522 to MH at University of Houston (Houston, TX) and to MY at Washington University (St. Louis, MO).
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/4/6
Y1 - 2010/4/6
N2 - The purpose of this research was to develop a sensitive and reproducible UPLC-MS/MS method to analyze matrine, an anticancer compound, and to use it to investigate its biopharmaceutical and pharmacokinetic behaviors in rats. A sensitive and fast UPLC-MS/MS method was successfully applied to determine matrine in rat plasma, intestinal perfusate, bile, microsomes, and cell incubation media. The absolute oral bioavailability of matrine is 17.1 ± 5.4% at a dose of 2 mg/kg matrine. Matrine at 10 μM was shown to have good permeability (42.5 × 10-6 cm/s) across the Caco-2 cell monolayer, and the ratio of PA-B to PB-A was approximately equal to 1 at two different concentrations (1 and 10 μM). Perfusion study showed that matrine displayed significant differences (P < 0.05) in permeability at different intestinal regions. The rank order of permeability was ileum (highest, Pw = 6.18), followed by colon (Pw = 2.07), duodenum (Pw = 0.61) and jejunum (Pw = 0.52). Rat liver microsome studies showed that CYP and UGTs were not involved in matrine metabolism. In conclusion, a sensitive and reliable method capable of measuring matrine in a variety of matrixes was developed and successfully used to determine absolute oral bioavailability of matrine in rats, transport across Caco-2 cell monolayers, absorption in rat intestine, and metabolism in rat liver microsomes.
AB - The purpose of this research was to develop a sensitive and reproducible UPLC-MS/MS method to analyze matrine, an anticancer compound, and to use it to investigate its biopharmaceutical and pharmacokinetic behaviors in rats. A sensitive and fast UPLC-MS/MS method was successfully applied to determine matrine in rat plasma, intestinal perfusate, bile, microsomes, and cell incubation media. The absolute oral bioavailability of matrine is 17.1 ± 5.4% at a dose of 2 mg/kg matrine. Matrine at 10 μM was shown to have good permeability (42.5 × 10-6 cm/s) across the Caco-2 cell monolayer, and the ratio of PA-B to PB-A was approximately equal to 1 at two different concentrations (1 and 10 μM). Perfusion study showed that matrine displayed significant differences (P < 0.05) in permeability at different intestinal regions. The rank order of permeability was ileum (highest, Pw = 6.18), followed by colon (Pw = 2.07), duodenum (Pw = 0.61) and jejunum (Pw = 0.52). Rat liver microsome studies showed that CYP and UGTs were not involved in matrine metabolism. In conclusion, a sensitive and reliable method capable of measuring matrine in a variety of matrixes was developed and successfully used to determine absolute oral bioavailability of matrine in rats, transport across Caco-2 cell monolayers, absorption in rat intestine, and metabolism in rat liver microsomes.
KW - Caco-2 cells
KW - Matrine
KW - Microsomes
KW - Pharmacokinetics
KW - Rat intestine perfusion
KW - UPLC-MS/MS
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U2 - 10.1016/j.jpba.2009.11.020
DO - 10.1016/j.jpba.2009.11.020
M3 - Article
C2 - 20034755
AN - SCOPUS:72749104889
VL - 51
SP - 1120
EP - 1127
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
SN - 0731-7085
IS - 5
ER -