A sensitive LC–MS/MS method to quantify methylergonovine in human plasma and its application to a pharmacokinetic study

•A rapid, accurate and robust HPLC–MS/MS assay for determining Methylergonovine in human plasma.•Optimization of reliable samples preparation and LC–MS/MS method suitable for Methylergonovine.•The method was validated and was successfully used to support clinical studies.•The first report for measuring Methylergonovine in human plasma by HPLC–MS/MS method.

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 500 μL 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 10 ng/mL with a lower limit of quantification (LLOQ) of 0.025 ng/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 0.2 mg dose of ME maleate. It is suitable for both preclinical and clinical studies on ME.