Wang Qing, Li Zi-jing, Sun Lu, Gao Li-ying, Li Ming-hui, Hao Jia-jia, Zhang Xin, Sun Yu-ming
School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116024, China.
Yao Xue Xue Bao. 2011 Apr;46(4):432-7.
A high sensitive and rapid method was developed for the analysis of lappaconitine in mouse plasma using liquid chromatography coupled to mass spectrometry (LC-MS). Detection was performed by positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 585 --> m/z 535 and m/z 356 --> m/z 192, for the quantification of lappaconitine and tetrahydropalmatine (internal standard, IS), respectively. The method was linear over the concentration range of 3.0-2000.0 ng x mL(-1). The lower limit of quantification was 3.0 ng x mL(-1). Intra- and inter-run precisions (RSD) were both less than 9.9% and accuracy (RE) within +/- 4.8%. After single intravenous injections of lappaconitine hydrobromide at 1.0, 2.0 and 4.0 mg x kg(-1), the elimination half-lives (t(1/2)) were 0.47, 0.48 and 0.49 h, and the areas under the curve (AUC(0-t)) were 55.5, 110.5 and 402.9 ng x h x mL(-1), separately. The pharmacokinetic profile of lappaconitine was linear at relatively lower dose levels (1.0-2.0 mg x kg(-1)). When the dose increased farther to 4.0 mg x kg(-1), the Vz and CL decreased, and the increase fold of the AUC was much larger than that of the dose.
建立了一种高灵敏度、快速的方法，用于采用液相色谱-质谱联用（LC-MS）分析小鼠血浆中的拉帕替尼。通过正离子电喷雾电离（ESI）在多反应监测（MRM）模式下进行检测，分别监测m/z 585 --> m/z 535和m/z 356 --> m/z 192的跃迁，以定量拉帕替尼和四氢巴马汀（内标，IS）。该方法在3.0-2000.0 ng x mL(-1)的浓度范围内呈线性。定量下限为3.0 ng x mL(-1)。批内和批间精密度（RSD）均小于9.9%，准确度（RE）在±4.8%以内。单次静脉注射氢溴酸拉帕替尼1.0、2.0和4.0 mg x kg(-1)后，消除半衰期（t(1/2)）分别为0.47、0.48和0.49 h，曲线下面积（AUC(0-t)）分别为55.5、110.5和402.9 ng x h x mL(-1)。拉帕替尼在相对较低剂量水平（1.0-2.0 mg x kg(-1)）下的药代动力学特征呈线性。当剂量进一步增加到4.0 mg x kg(-1)时，Vz和CL降低，AUC的增加倍数远大于剂量的增加倍数。
