Kang An, Xie Tong, Zhu Dong, Dong Yu, Wen Hongmei, Pei Yuqiong, Shan Jinjun, Di Liuqing
Jiangsu Key Laboratory of Pediatric Respiratory Disease, State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, China.
Key Laboratory for Functional Substance of Chinese Medicine, Nanjing, China.
Biomed Chromatogr. 2017 Oct;31(10). doi: 10.1002/bmc.3977. Epub 2017 Apr 18.
Pyranocoumarins are the main constitutes in Peucedanum praeruptorum Dunn and possess various biological activities. In this article, we developed and validated a rapid and sensitive liquid chromatography-tandem mass spectrometry method for the targeted quantification of the pyranocoumarins, praeruptorin A, praeruptorin B and praeruptorin E, and khellactone, which is a common metabolite of these pyranocoumarins in rat plasma samples. We then performed a comparative pharmacokinetic study of these pyranocoumarins and khellactone in normal and lipopolysaccharide-induced acute lung injury (ALI) in rats following oral administration of P. praeruptorum Dunn extracts. Calibration curves gave desirable linearity (r > 0.99) and the lower limit of quantifications were sufficient for quantitative analysis. The precision and accuracy were assessed by intra-batch and inter-batch assays, and the relative standard deviations were all within 10.23% and the accuracy (relative error) was between -5.52% and 8.68%. The extraction recoveries, matrix effects and stability were also acceptable. The pharmacokinetic study revealed that the area under the concentration-time curve (0-t) of khellactone in ALI rats was significantly decreased compared with the normal rats. Meanwhile, the systemic exposures of these pyranocoumarins were slightly higher in the ALI rats than those in normal rats were. The pharmacokinetic study in the pathological state might provide information that was more comprehensive to guide the clinical usage of P. praeruptorum Dunn.
吡喃香豆素是白花前胡的主要成分，具有多种生物活性。在本文中，我们开发并验证了一种快速灵敏的液相色谱-串联质谱法，用于靶向定量测定大鼠血浆样品中的吡喃香豆素、白花前胡甲素、白花前胡乙素和白花前胡丙素以及凯林内酯（这些吡喃香豆素的常见代谢产物）。然后，我们对白花前胡提取物口服给药后，正常大鼠和脂多糖诱导的急性肺损伤（ALI）大鼠体内的这些吡喃香豆素和凯林内酯进行了比较药代动力学研究。校准曲线具有良好的线性（r＞0.99），定量下限足以进行定量分析。通过批内和批间测定评估精密度和准确度，相对标准偏差均在10.23%以内，准确度（相对误差）在-5.52%至8.68%之间。提取回收率、基质效应和稳定性也均可接受。药代动力学研究表明，与正常大鼠相比，ALI大鼠体内凯林内酯的浓度-时间曲线下面积（0-t）显著降低。同时，这些吡喃香豆素在ALI大鼠体内的全身暴露量略高于正常大鼠。病理状态下的药代动力学研究可能提供更全面的信息，以指导白花前胡的临床应用。
