Chen Feng, Li Hai-Long, Tan Yin-Feng, Guan Wei-Wei, Li Yong-Hui, Zhang Jun-Qing
School of Pharmacy, Hainan Medical University, Hainan Provincial Key Laboratory of R&D of Tropical Herbs, Haikou 571101, China.
Chem Cent J. 2014 Jan 14;8(1):2. doi: 10.1186/1752-153X-8-2.
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.
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.
The proposed method is sensitive and reliable. It is hoped that this new method will prove useful for the future PK studies.
姜辣素A具有多种有益的生物学效应。然而，迄今为止，姜辣素A的药代动力学（PK）数据仍然未知。此外，文献中尚未报道生物样品中姜辣素A的定量方法。因此，在本研究中，我们旨在开发一种新方法，用于快速、高效和准确地评估血浆中姜辣素A的浓度，作为促进姜辣素A的PK评估的一种手段。
开发并验证了一种液相色谱-电喷雾电离-串联质谱（LC-ESI-MS/MS）方法，用于测定大鼠血浆中的姜辣素A。对质谱和色谱条件进行了优化。血浆样品用甲醇进行蛋白沉淀预处理。在Phenomenex Luna C18柱上进行LC分离，采用梯度洗脱，流动相由含0.5 mM甲酸（HCOOH）的甲醇-水组成，流速为0.28 mL/min。在正离子多反应监测模式（MRM）下采集ESI-MS谱。用于姜辣素A和姜辣素B的MRM的前体-产物离子对分别为m/z 313.1→137.0和311.2→117.1。低浓度的HCOOH减少了基质成分引起的离子抑制，并明显提高了分析灵敏度。姜辣素A在很宽的浓度范围内显示出良好的线性（r＞0.99）。发现准确度、精密度、稳定性和线性均在可接受标准范围内。该新方法成功应用于分析单次口服缩泉胶囊后大鼠血浆中母体姜辣素A的浓度。观察到母体姜辣素A的全身暴露较低。
所提出的方法灵敏且可靠。希望这种新方法将被证明对未来的PK研究有用。
