Riggs K W, Szeitz A, Rurak D W, Mutlib A E, Abbott F S, Axelson J E
Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
J Chromatogr B Biomed Appl. 1994 Oct 14;660(2):315-25. doi: 10.1016/0378-4347(94)00314-9.
A modified gas chromatographic-mass spectrometric (GC-MS) assay has been developed to quantitate metoclopramide (MCP) and two of its metabolites [monodeethylated-MCP (mdMCP), dideethylated-MCP (ddMCP)] in the plasma, bile and urine of sheep. The heptafluorobutyryl derivatives of the compounds were formed and quantitated using electron-impact ionization in the selected-ion monitoring mode (MCP, m/z 86, 380; mdMCP, m/z 380 and ddMCP, m/z 380). No interference was observed from endogenous compounds following the extraction of various biological fluids obtained from non-pregnant sheep. Sample preparation has been simplified and the method is more selective and sensitive (2 fold) than our previous assay using electron-capture detection. The limit of quantitation for MCP, mdMCP and ddMCP was 1 ng/ml in plasma, urine and bile, requiring 0.5 ml of sample. This represents 2.5 pg of the analytes at the detector. The standard curves were linear over a working range of 1-40 ng/ml. Absolute recoveries in plasma ranged from 76.5-94.7%, 79.2-96.8%, 80.3-102.2% for MCP, mdMCP and ddMCP, respectively. In urine, recoveries ranged from 56.5-87.8%, 61.5-87.5%, 62.6-90.2% for MCP, mdMCP and ddMCP, respectively. Recoveries in bile ranged from 83.5-100.9%, 78.5-90.5%, 66.9-79.2% for MCP, mdMCP and ddMCP, respectively. Overall intra-day precision ranged from 2.9% for MCP in plasma to 12.6% for mdMCP in bile. Overall inter-day precision ranged from 5.9% for MCP in urine to 14.9% for ddMCP in bile. Bias was the greatest at the 1 ng/ml concentration in all biological fluids ranging from a low of 2.4% for mdMCP in plasma to a high of 11.9% for ddMCP in urine. Applicability of the assay for pharmacokinetic studies of MCP, mdMCP and ddMCP in the plasma and urine of a non-pregnant ewe is demonstrated.
已开发出一种改良的气相色谱 - 质谱联用（GC - MS）分析法，用于定量绵羊血浆、胆汁和尿液中的甲氧氯普胺（MCP）及其两种代谢物[单去乙基 - MCP（mdMCP）、双去乙基 - MCP（ddMCP）]。这些化合物的七氟丁酰衍生物在选定离子监测模式下使用电子轰击电离进行形成和定量（MCP，m/z 86、380；mdMCP，m/z 380；ddMCP，m/z 380）。从非妊娠绵羊获取的各种生物流体提取后，未观察到内源性化合物的干扰。样品制备得到简化，该方法比我们先前使用电子捕获检测的方法更具选择性和敏感性（提高了2倍）。MCP、mdMCP和ddMCP在血浆、尿液和胆汁中的定量限为1 ng/ml，每个样品需要0.5 ml。这在检测器处代表2.5 pg的分析物。标准曲线在1 - 40 ng/ml的工作范围内呈线性。MCP、mdMCP和ddMCP在血浆中的绝对回收率分别为76.5 - 94.7%、79.2 - 96.8%、80.3 - 102.2%。在尿液中，回收率分别为56.5 - 87.8%、61.5 - 87.5%、62.6 - 90.2%。在胆汁中，回收率分别为83.5 - 100.9%、78.5 - 90.5%、66.9 - 79.2%。总体日内精密度范围从血浆中MCP的2.9%到胆汁中mdMCP的12.6%。总体日间精密度范围从尿液中MCP的5.9%到胆汁中ddMCP的14.9%。在所有生物流体中，1 ng/ml浓度下偏差最大，范围从血浆中mdMCP的低2.4%到尿液中ddMCP的高11.9%。证明了该分析法在非妊娠母羊血浆和尿液中MCP、mdMCP和ddMCP药代动力学研究中的适用性。
