title: Development of a SPE-LC/MS/MS method for simultaneous quantification of baicalein, wogonin, oroxylin A and their glucuronides baicalin, wogonoside and oroxyloside in rats and its application to brain uptake and plasma pharmacokinetic studies.
abstract: This study aims to identify and quantify the six major bioactive flavones of the traditional Chinese medicine Scutellariae Radix (RS), including baicalein, baicalin, wogonin, wogonoside, oroxylin A and oroxyloside in rat after oral administration of a standardized RS extract. A novel, sensitive and selective method for simultaneous determination of these six analytes in rat brain and plasma using solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC/MS/MS) was developed and fully validated. The lower limits of quantification (LLOQs) for the six RS flavones in brain tissue were 0.02nmol/g. The LLOQs in plasma were 0.005nmol/ml for B, W and OA, 0.025nmol/ml for WG and OAG, and 0.1875nmol/ml for BG. The current study provides novel evidence of the presence of all the tested RS flavones and an isoform of BG (BG', probably baicalein-6-O-glucuronide) in the rat brain after oral administration of RS extract, suggesting their ability to permeate through the blood-brain barrier. The method was also successfully applied to the pharmacokinetic study of all these analytes in plasma after oral administration of RS extract (300mg/kg) to Sprague-Dawley rats. The developed assay method provides a useful tool for both preclinical and clinical investigations on the disposition of RS flavones in brain and plasma.
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: Sophia Yui Kau
authors.initials: SY
authors.lastname: Fong
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: Yin Cheong
authors.initials: YC
authors.lastname: Wong
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. Electronic address: joanzuo@cuhk.edu.hk.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D044950:Flavanones / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D047309:Flavones / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D005419:Flavonoids / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D005960:Glucosides / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D020719:Glucuronides / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D044950:Flavanones; D047309:Flavones; D005419:Flavonoids; D005960:Glucosides; D020719:Glucuronides; C000596749:oroxylin A-7-O-glucuronide; C038044:baicalin; C006680:baicalein; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; C473995:wogonoside; C085514:wogonin
keywords: Brain; Glucuronides; LC/MS/MS; Plasma; Scutellariae Radix