title: Application of a liquid chromatography-tandem mass spectrometry method to the pharmacokinetics, tissue distribution and excretion studies of brazilin in rats.
abstract: Brazilin is an important constituent of Caesalpinia sappan L., and has several bioactivities. In this study, a rapid and sensitive analytical method based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been developed for the determination of brazilin in rat plasma, urine, feces and tissues (brain, heart, liver, lung and kidney and spleen). Biological samples were processed with ethyl acetate containing 5% formic acid extraction, and salicylic acid (SA) was chosen as the internal standard (IS). The separation of brazilin was achieved on an Inspire C18 column (4.6mm×150mm, 5μm) with a mobile phase consisting of methanol/5mM ammonium acetate (80:20, v/v). The MS/MS detection was carried out by monitoring the fragmentation of m/z 285.1→163.0 for brazilin and m/z 137.1→93.1 for SA on a triple quadrupole mass spectrometer. The total run time was only 5.0min. The analyte showed good linearity over a wide concentration range (R(2)>0.995) and its lower limit of quantification was 2ng/mL. The accuracy and precision ranged from 97.1 to 103.3% and 1.7 to 9.1%, respectively. Recoveries (78.9-93.8%) and matrix effects (81.0-97.8%) were satisfactory in all the biological matrices examined. Stability studies (86.4-99.8%) showed that brazilin was stable during the assay procedure and long-term storage. The assay was successfully applied to plasma pharmacokinetics, tissue distribution and excretion study of rats. The pharmacokinetic parameters, such as half-life, mean residence time, maximum concentration were determined. These preclinical data of brazilin would be useful for the clinical reference.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Jia
authors.forename: Hujun
authors.initials: H
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Dou
authors.forename: Chengtao
authors.initials: C
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Ge
authors.forename: Ningjuan
authors.initials: N
authors.lastname: Chi
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Wenli
authors.initials: W
authors.lastname: Hai
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D001578:Benzopyrans; C044362:brazilin