Kim Young Hoon, Ji Hye Young, Lee Seonkyoung, Yi Kyu Yang, Kim You Sun, Lee Kyung Hee, Lee Hye Suk
Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea.
Biomed Chromatogr. 2007 Aug;21(8):810-5. doi: 10.1002/bmc.806.
A liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed for the determination of a selective Na(+)/H(+) exchanger inhibitor 4-cyano(benzo[b]thiophene-2-carbonyl)guanidine (KR-33028) in rat plasma. KR-33028 and the internal standard, linezolid, were extracted from rat plasma with ethyl acetate at neutral pH. The analytes were separated on an XBridge C(18) column with a mixture of methanol-0.1% formic acid (35:65, v/v) as mobile phase and detected using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r = 0.9998) over the concentration range of 2.0-1000 ng/mL. The coefficients of variation of intra- and inter-assay were 1.3-6.8% and the relative error was 0.8-5.0%. The recoveries of KR-33028 and linezolid were 70.5 and 84.6%, respectively. The lower limit of quantification for KR-33028 was 2.0 ng/mL using 50 microL plasma sample. This method was successfully applied to the pharmacokinetic study of KR-33028 in rats.
建立了一种液相色谱-串联质谱（LC/MS/MS）法，用于测定大鼠血浆中选择性Na(+)/H(+)交换抑制剂4-氰基（苯并[b]噻吩-2-羰基）胍（KR-33028）。KR-33028和内标利奈唑胺在中性pH条件下用乙酸乙酯从大鼠血浆中萃取。分析物在XBridge C(18)柱上分离，以甲醇-0.1%甲酸（35:65，v/v）混合物为流动相，并采用电喷雾电离串联质谱在多反应监测模式下进行检测。标准曲线在2.0 - 1000 ng/mL浓度范围内呈线性（r = 0.9998）。批内和批间变异系数分别为1.3 - 6.8%，相对误差为0.8 - 5.0%。KR-33028和利奈唑胺的回收率分别为70.5%和84.6%。使用50 μL血浆样品时，KR-33028的定量下限为2.0 ng/mL。该方法成功应用于KR-33028在大鼠体内的药代动力学研究。
