National Institute of Legal Medicine-South Branch, Rua Manuel Bento de Sousa n(o)3, 1169-201 Lisbon, Portugal.
J Pharm Biomed Anal. 2012 Dec;71:198-201. doi: 10.1016/j.jpba.2012.08.005. Epub 2012 Aug 16.
Misoprostol is a pharmaceutical synthetic compound, analog of prostaglandin E1, frequently used as an abortifacient in not medically supervised or self-induced abortions, particularly in countries with restrictive abortion laws representing a serious public health problem. The aim of this study was to develop and validate a sensitive analytical method for the determination of misoprostol acid in whole blood samples. The samples were prepared by SPE and the chromatographic separation was performed by UPLC-MS/MS using ESI- and MRM mode with an Acquity UPLC(®) BEH C18 (50mm×2.1mm i.d., 1.7μm) column using a methanol-ammonium 0.1% solution gradient in a total run time of 7.0min. The method showed to be selective and linear in range 25-2000ng/L. The LOD and LOQ were 10ng/L and 25ng/L, respectively. The recovery ranged from 89 to 97%. No carryover and significant matrix effect were observed. The intra- and inter-assay precisions and the inter-assay accuracy results were 4.0% and 5.4%, 5.5% and 4.1%, and -1.4% and -2.8%, for the concentrations 50 and 500ng/L, respectively. The method developed allows the analysis of misoprostol acid in whole blood samples with adequate sensitivity to the concentration range obtained from therapeutic doses. The method was successfully used in a controlled misoprostol administration study and has been applied in our laboratory in the forensic toxicology field.
米索前列醇是一种药物合成化合物，前列腺素 E1 的类似物，常用于未经医学监督或自行进行的流产中作为堕胎药，尤其是在那些堕胎法限制严格的国家，这是一个严重的公共卫生问题。本研究旨在开发和验证一种用于测定全血样品中米索前列醇酸的灵敏分析方法。样品通过 SPE 制备，通过 UPLC-MS/MS 进行色谱分离，采用 ESI- 和 MRM 模式，使用 Acquity UPLC(®) BEH C18（50mm×2.1mm id，1.7μm）柱，在总运行时间为 7.0min 的情况下，采用甲醇-铵 0.1%溶液梯度。该方法表现出选择性和在 25-2000ng/L 范围内的线性。LOD 和 LOQ 分别为 10ng/L 和 25ng/L。回收率范围为 89-97%。未观察到拖尾和显著的基质效应。日内和日间精密度和日间准确度结果分别为 50 和 500ng/L 浓度时的 4.0%和 5.4%、5.5%和 4.1%以及-1.4%和-2.8%。该方法能够对治疗剂量范围内获得的浓度进行全血样品中米索前列醇酸的分析，具有足够的灵敏度。该方法已成功应用于控制米索前列醇给药研究，并已在我们实验室的法医毒理学领域得到应用。
