title: A sensitive LC-MS/MS method to quantify methylergonovine in human plasma and its application to a pharmacokinetic study.
abstract: Methylergonovine (ME) is a semisynthetic ergot alkaloid that is used for the treatment and prophylaxis of postpartum hemorrhage. In recent years, methylergonovine has been effective in the control of refractory headaches and is likely to be employed as chemosensitizers for cancer. However, this alkaloid sometimes causes elevated blood pressure. Therefore, a sensitive and accurate method for the quantification of this drug in biological matrices is necessary. In this study, ME was extracted from 500μL plasma samples by a liquid-liquid extraction under alkaline conditions and detected using positive multi-reaction-monitoring mode (+MRM) mass spectrometry. The method was validated according to US FDA guidelines and covered a working range from 0.025 to 10ng/mL with a lower limit of quantification (LLOQ) of 0.025ng/mL. In conclusion, a rapid, sensitive, selective and accurate quantification by an LC-MS/MS method was developed and successfully applied to a clinical pharmacokinetics study in female volunteers after a single intramuscular injection or oral administration of a 0.2mg dose of ME maleate. It is suitable for both preclinical and clinical studies on ME.
authors.affiliation: School of Pharmaceutical Sciences of Shandong University, No. 44 West Wenhua Road, Jinan 250012 China. Electronic address: may@sdu.edu.cn.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Pharmaceutical Sciences of Shandong University, No. 44 West Wenhua Road, Jinan 250012 China.
authors.forename: Qichao
authors.initials: Q
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences of Shandong University, No. 44 West Wenhua Road, Jinan 250012 China.
authors.forename: Dongming
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Biological Science, College of Liberal Arts and Sciences of University of Connecticut, 2131 Hillside Rd, Storrs, CT 06269, United States.
authors.forename: Bowen
authors.initials: B
authors.lastname: Ma
authors.affiliation: The Second Hospital of Shandong University, No. 247 Beiyuan Avenue, Jinan 250033, China.
authors.forename: Hengli
authors.initials: H
authors.lastname: Zhao
authors.affiliation: The Second Hospital of Shandong University, No. 247 Beiyuan Avenue, Jinan 250033, China.
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Fang
authors.affiliation: The Second Hospital of Shandong University, No. 247 Beiyuan Avenue, Jinan 250033, China.
authors.forename: Haisheng
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences of Shandong University, No. 44 West Wenhua Road, Jinan 250012 China; Department of Natural Products Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan 250012, China. Electronic address: louhongxiang@sdu.edu.cn.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Lou
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D016014:Linear Models; D008755:Methylergonovine / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D008755:Methylergonovine
keywords: HPLC–MS/MS; Human plasma; Methylergonovine; Pharmacokinetics