title: Simultaneous determination of bioactive components in essential oil of Xiang-Fu-Si-Wu Formula in Beagle dog plasma by UPLC-MS/MS and its application to pharmacokinetics.
abstract: A highly sensitive and rapid ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for simultaneous quantification of the three main bioactive compounds, i.e., ligustilide, dehydrocostuslactone and α-cyperone in dog plasma after oral administration of the essential oil of Xiang-Fu-Si-Wu Formula (XEO). Clarithromycin was used as an internal standard (IS). Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100mm×2.1mm, 1.7μm) at a flow rate of 0.4mLmin(-1), using 0.1% formic acid-acetonitrile as mobile phase. The MS/MS ion transit ions monitored were 190.5→90.9 for ligustilide, 231.1→185.1 for dehydrocostuslactone, 219.2→123.0 for α-cyperone and 748.5→158.1 for IS. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. The lower limit of quantification (LLOQ) achieved was 5.12ng/mL for ligustilide, 1.06ng/mL for dehydrocostuslactone and 1.89ng/mL for α-cyperone, respectively, and the calibration curves obtained were linear (r>0.99) over the concentration range approximately 1-1000ng/mL. The intra- and inter-day precision was less than 15% and the accuracy was within ±9.2%. After validation, this method was successfully applied to a pharmacokinetic study where dogs were orally given 0.3g/kg XEO, equivalent to 183.6mg/kg of ligustilide, 5.0mg/kg of dehydrocostuslactone and 26.2mg/kg of α-cyperone, respectively.
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210046, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.forename: Zhenhao
authors.initials: Z
authors.lastname: Li
authors.forename: Dawei
authors.initials: D
authors.lastname: Qian
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Er-Xin
authors.initials: EX
authors.lastname: Shang
authors.forename: Jin-Ao
authors.initials: JA
authors.lastname: Duan
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D005260:Female; D007783:Lactones / Q000097:blood / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012717:Sesquiterpenes / Q000097:blood / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D007783:Lactones; D012717:Sesquiterpenes; C027820:ligustilide; C083030:dehydrocostus lactone; D015107:4-Butyrolactone