title: Development of a fast LC-MS/MS method for quantification of rilmenidine in human serum: elucidation of fragmentation pathways by HRMS.
abstract: Rilmenidine is an alpha 2 adrenoreceptor agonist used in the treatment of mild and moderate hypertension. In this study, a fast and accurate liquid chromatographic method with tandem mass spectrometric detection has been validated in order to assure quantification of rilmenidine in human serum. The fragmentation pathway of protonated rilmenidine was studied using high-resolution mass spectrometry (HRMS). This study compared selectivity, linearity, accuracy, precision, extraction efficiency, matrix effect and sensitivity using common liquid-liquid extraction (LLE) and solid-phase extraction (SPE) procedures. The limit of quantitation for both extraction techniques was 0.1 ng/ml. Several differences between the LLE and SPE have been observed in terms of linearity, accuracy, precision and matrix effect. Additionally, the advantages of SPE included less manual work load and increased recovery of rilmenidine in human serum to approximately 80% (LLE, 57%). The developed method involving SPE was found to be accurate (relative error (RE) < 5%), reproducible (relative standard deviation, RSD < 7%), robust and suitable for quantitative analysis of rilmenidine in serum samples obtained from patients under antihypertensive treatment.
authors.affiliation: Institute of Forensic Medicine and Toxicology, 1st Faculty of Medicine, Charles University in Prague, 121 08 Prague 2, Czech Republic. lukas.chytil@lf1.cuni.cz
authors.forename: Lukáš
authors.initials: L
authors.lastname: Chytil
authors.forename: Josef
authors.initials: J
authors.lastname: Cvačka
authors.forename: Věra
authors.initials: V
authors.lastname: Marešová
authors.forename: Branislav
authors.initials: B
authors.lastname: Štrauch
authors.forename: Jiří
authors.initials: J
authors.lastname: Widimský
authors.forename: Martin
authors.initials: M
authors.lastname: Štícha
authors.forename: Ondřej
authors.initials: O
authors.lastname: Slanař
mesh_terms: D000959:Antihypertensive Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016018:Least-Squares Analysis; D010080:Oxazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D000077769:Rilmenidine; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000959:Antihypertensive Agents; D010080:Oxazoles; D000077769:Rilmenidine