title: Validated method for the determination of misoprostol acid in whole blood by ultra performance liquid chromatography-tandem mass spectrometry.
abstract: 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.
authors.affiliation: National Institute of Legal Medicine-South Branch, Rua Manuel Bento de Sousa n(o)3, 1169-201 Lisbon, Portugal. ssimoes@dlinml.mj.pt
authors.forename: Susana Sadler
authors.initials: SS
authors.lastname: Simões
authors.forename: Antonio Castañera
authors.initials: AC
authors.lastname: Ajenjo
authors.forename: Mário João
authors.initials: MJ
authors.lastname: Dias
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000097:blood / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D016595:Misoprostol / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D016595:Misoprostol; C047042:misoprostol acid