Validated method for the determination of misoprostol acid in whole blood by ultra performance liquid chromatography–tandem mass spectrometry

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 (50 mm × 2.1 mm i.d., 1.7 μm) column using a methanol–ammonium 0.1% solution gradient in a total run time of 7.0 min. The method showed to be selective and linear in range 25–2000 ng/L. The LOD and LOQ were 10 ng/L and 25 ng/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 500 ng/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.