title: Biopharmaceutical and pharmacokinetic characterization of matrine as determined by a sensitive and robust UPLC-MS/MS method.
abstract: 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 2mg/kg matrine. Matrine at 10microM was shown to have good permeability (42.5x10(-6)cm/s) across the Caco-2 cell monolayer, and the ratio of P(A-B) to P(B-A) was approximately equal to 1 at two different concentrations (1 and 10microM). 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, P(w)=6.18), followed by colon (P(w)=2.07), duodenum (P(w)=0.61) and jejunum (P(w)=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.
authors.affiliation: Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, 1441 Moursund Street, Houston, TX 77030, United States.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.forename: Taijun
authors.initials: T
authors.lastname: Yin
authors.forename: Kaustubh H
authors.initials: KH
authors.lastname: Kulkarni
authors.forename: Yang
authors.initials: Y
authors.lastname: Teng
authors.forename: Ming
authors.initials: M
authors.lastname: You
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D000470:Alkaloids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D001682:Biological Availability; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010477:Perfusion; D010539:Permeability; D011807:Quinolizines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D011807:Quinolizines; D000093842:Matrines