Im So Hee, Park Myoung Joo, Seo Hyewon, Choi Sung Heum, Kim Sang Kyum, Ahn Sung-Hoon
Department of Drug Discovery Platform Technology, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea; College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Department of Drug Discovery Platform Technology, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.
J Chromatogr B Analyt Technol Biomed Life Sci. 2014 May 1;958:117-23. doi: 10.1016/j.jchromb.2014.03.020. Epub 2014 Mar 24.
The object of the present study was to develop and validate an assay method of mesoridazine in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma samples from rats were prepared by simple protein precipitation and injected onto the LC-MS/MS system for quantification. Mesoridazine and chlorpromazine as an internal standard (IS) were separated by a reversed phase C18 column. A mobile phase was composed of 10mM ammonium formate in water and acetonitrile (ACN) (v/v) by a linear gradient system, increasing the percentage of ACN from 2% at 0.4min to 98% at 2.5min with 4min total run time. The ion transitions monitored in positive-ion mode M+H of multiple-reaction monitoring (MRM) were m/z 387>126 for mesoridazine and m/z 319>86 for IS. The detector response was specific and linear for mesoridazine at concentrations within the range 0.001-4μg/ml and the correlation coefficient (R(2)) was greater than 0.999 and the signal-to-noise ratios for the samples were ≥10. The intra- and inter-day precision and accuracy of the method were determined to be within the acceptance criteria for assay validation guidelines. The matrix effects were approximately 101 and 99.5% from rat plasma for mesoridazine and chlorpromazine, respectively. Mesoridazine was stable under various processing and/or handling conditions. Mesoridazine concentrations were readily measured in rat plasma samples after intravenous and oral administration. This assay method can be practically useful to the pharmacokinetic and/or toxicokinetic studies of mesoridazine.
本研究的目的是开发并验证一种使用液相色谱 - 串联质谱法（LC-MS/MS）测定大鼠血浆中美索达嗪的方法。大鼠血浆样本通过简单的蛋白沉淀法制备，然后注入LC-MS/MS系统进行定量分析。美索达嗪和作为内标（IS）的氯丙嗪通过反相C18柱进行分离。流动相由含10mM甲酸铵的水和乙腈（ACN）（v/v）组成，采用线性梯度系统，在4分钟的总运行时间内，将ACN的百分比从0.4分钟时的2%增加到2.5分钟时的98%。在多反应监测（MRM）的正离子模式M+H下监测的离子跃迁，美索达嗪为m/z 387>126，内标为m/z 319>86。在0.001 - 4μg/ml浓度范围内，美索达嗪的检测器响应具有特异性且呈线性，相关系数（R(2)）大于0.999，样品的信噪比≥10。该方法的日内和日间精密度及准确度均在分析方法验证指南的可接受标准范围内。美索达嗪和氯丙嗪在大鼠血浆中的基质效应分别约为101%和99.5%。美索达嗪在各种处理和/或操作条件下均稳定。静脉注射和口服给药后，大鼠血浆样本中的美索达嗪浓度易于测定。这种分析方法对于美索达嗪的药代动力学和/或毒代动力学研究具有实际应用价值。
