title: Evaluating misoprostol content in pregnant women with hourly oral administration during labor induction by microElution solid phase extraction combined with liquid chromatography tandem mass spectrometry.
abstract: Misoprostol is a widely used alternative of prostaglandin for labor induction. Based on previous studies, we envision that small and frequent oral dosage of misoprostol is an effective method for labor induction. To monitor the misoprostol content during labor induction, a rapid, sensitive, and selective microElution solid phase extraction (μElution SPE) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. Using μElution SPE could minimize the sample consumption and elution volume in order to maximize the sample enrichment and throughput. The misoprostol acid, a metabolite of misoprostol, was gradient separated in a Bidentate C18 column, then quantified by highly-selective reaction monitoring (H-SRM) in a total run time of 6min. The developed method was optimized and validated in human plasma, and showed linear range of 0.01-10ng/mL. The limit of detection (LOD) was 0.001ng/mL. The recovery ranged from 89.0 to 96.0%, and no significant matrix effect or carryover was observed. The precision, accuracy and stability were met with the criteria of U.S. FDA guidance. The developed method was successfully applied to evaluate misoprostol concentration during labor induction in pregnant women. The concentration-time profiles approves that hourly oral administration of misoprostol is a safe and effective method without drug accumulation for labor induction.
authors.affiliation: Department of Chemistry, National Chung Hsing University, Taichung 40227, Taiwan, ROC.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Hung
authors.affiliation: School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC; Department of Obstetrics and Gynecology, China Medical University Beigang Hospital, Yunlin 65152, Taiwan, ROC; Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin 65152 Taiwan, ROC.
authors.forename: Shi-Yann
authors.initials: SY
authors.lastname: Cheng
authors.affiliation: Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin 65152 Taiwan, ROC.
authors.forename: Tzu-Min
authors.initials: TM
authors.lastname: Chan
authors.affiliation: Department of Chemistry, National Chung Hsing University, Taichung 40227, Taiwan, ROC. Electronic address: mrlee@dragon.nchu.edu.tw.
authors.forename: Maw-Rong
authors.initials: MR
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D007751:Labor, Induced; D057230:Limit of Detection; D016014:Linear Models; D016595:Misoprostol / Q000008:administration & dosage / Q000097:blood*; D010120:Oxytocics / Q000008:administration & dosage / Q000097:blood*; D011247:Pregnancy; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D010120:Oxytocics; D016595:Misoprostol
keywords: Labor induction; Liquid chromatography tandem mass spectrometry; Misoprostol acid; highly-selective reaction monitoring; microElution solid phase extraction