Cui Shuangjin, Feng Fang, Ma Ming, Liu Han, Chen Yun
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jul 1;854(1-2):143-51. doi: 10.1016/j.jchromb.2007.04.019. Epub 2007 Apr 25.
A highly sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of the prodrug fosinopril and its major active metabolite fosinoprilat for pharmacokinetic studies in healthy subjects. In order to get the lower limit of quantification (LLOQ), especially for analysis of fosinopril, key points of the method have been investigated including chromatographic conditions and selection of LC-MS/MS conditions. The analytes were extracted from plasma samples by liquid-liquid extraction, separated on a reversed-phase C(8) column using gradient procedure, and detected by tandem mass spectrometry with a triple quadrupole ionization interface. The analytes and internal standard zaleplon were detected using positive electrospray ionization (ESI) in the SRM mode. The LLOQ of the method down to 0.1 ng mL(-1) for fosinopril and 1.0 ng mL(-1) for fosinoprilat were identifiable and reproducible. The standard calibration curves for both fosinopril and fosinoprilat were linear over the ranges of 0.1-15.0 and 1.0-700 ng mL(-1) in human plasma, respectively. The within- and between-batch precisions (relative standard deviation (RSD)%) and the accuracy were acceptable. The validated method was successfully applied to reveal the pharmacokinetic properties of fosinopril and fosinoprilat after oral administration.
建立了一种高灵敏度和高选择性的液相色谱-串联质谱（LC-MS/MS）方法，并进行了验证，用于同时测定前药福辛普利及其主要活性代谢物福辛普利拉，以用于健康受试者的药代动力学研究。为了获得定量下限（LLOQ），特别是对于福辛普利的分析，研究了该方法的关键点，包括色谱条件和LC-MS/MS条件的选择。通过液-液萃取从血浆样品中提取分析物，使用梯度程序在反相C(8)柱上进行分离，并通过带有三重四极杆电离接口的串联质谱进行检测。分析物和内标扎来普隆在SRM模式下使用正电喷雾电离（ESI）进行检测。该方法对福辛普利的LLOQ低至0.1 ng mL(-1)，对福辛普利拉的LLOQ为1.0 ng mL(-1)，可识别且可重现。福辛普利和福辛普利拉在人血浆中的标准校准曲线分别在0.1-15.0和1.0-700 ng mL(-1)范围内呈线性。批内和批间精密度（相对标准偏差（RSD）%）以及准确度均可接受。经过验证的方法成功应用于揭示口服给药后福辛普利和福辛普利拉的药代动力学特性。
