title: Validated method to measure yakuchinone A in plasma by LC-MS/MS and its application to a pharmacokinetic study in rats.
abstract: BACKGROUND
  Yakuchinone A has a plethora of beneficial biological effects. However, the pharmacokinetic (PK) data of yakuchinone A still remain unknown so far. Furthermore, the quantification of yakuchinone A in biological samples has not been reported in the literature. Therefore, in the present study we aimed to develop a new method for the fast, efficient and accurate assessment of yakuchinone A concentration in plasma, as a means for facilitating the PK evaluation of yakuchinone A.
  
  
  RESULTS
  A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the determination of yakuchinone A in rat plasma. Mass spectrometric and chromatographic conditions were optimized. Plasma samples were pretreated by protein precipitation with methanol. LC separation was performed on a Phenomenex Luna C18 column with gradient elution using a mobile phase consisting of methanol-water containing 0.5 mM formic acid (HCOOH) at a flow rate of 0.28 mL/min. ESI-MS spectra were acquired in positive ion multiple reaction monitoring mode (MRM). The precursor-to-product ion pairs used for MRM of yakuchinone A and yakuchinone B were m/z 313.1 → 137.0 and 311.2 → 117.1, respectively. Low concentration of HCOOH reduced the ion suppression caused by matrix components and clearly improved the analytical sensitivity. Yakuchinone A showed good linearity over a wide concentration range (r > 0.99). The accuracy, precision, stability and linearity were found to be within the acceptable criteria. This new method was successfully applied to analyze the rat plasma concentration of parent yakuchinone A after a single oral administration of SuoQuan capsules. Low systemic exposure to parent yakuchinone A was observed.
  
  
  CONCLUSIONS
  The proposed method is sensitive and reliable. It is hoped that this new method will prove useful for the future PK studies.
authors.affiliation: School of Pharmacy, Hainan Medical University, Hainan Provincial Key Laboratory of R&D of Tropical Herbs, Haikou 571101, China. cy.chen508@gmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Li
authors.forename: Yin-Feng
authors.initials: YF
authors.lastname: Tan
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Guan
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Li
authors.forename: Jun-Qing
authors.initials: JQ
authors.lastname: Zhang