title: Application of a novel liquid chromatography/tandem mass spectrometry method for the determination of antazoline in human plasma: Result of ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study.
abstract: Antazoline is a first-generation antihistaminic agent with antiarrhythmic quinidine-like properties. In some countries, it is widely used for termination of cardiac arrhythmias, especially atrial fibrillation (AF). However, no human pharmacokinetic studies have been conducted with intravenous antazoline. The aim of our study was to develop and validate a novel liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the determination of antazoline in human plasma: the ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study. Antazoline was extracted from plasma using liquid-liquid extraction. The concentration of the analyte was measured by LC-MS/MS with xylometazoline as an internal standard. The method was validated for linearity, precision, accuracy, stability (freeze/thaw stability, stability in autosampler, short and long term stability), dilution integrity and matrix effect. The analyzed validation criteria were fulfilled. The method was applied to a pharmacokinetic study involving 10 healthy volunteers. Following a single intravenous dose of antazoline mesylate (100 mg), the plasma concentration profile showed a relative fast elimination with a terminal elimination half-life of 2.29 h. A relatively high volume of distribution was observed (Vss=315 L). The values of mean residence time (MRT∞), area under the curve (AUC∞) and clearance were 3.45 h, 0.91 mg h L(-1) and 80.5 L h(-1), respectively. One volunteer showed significant differences in pharmacokinetic parameters. In conclusion, the proposed new LC-MS/MS method was successfully used for the first time for the determination of antazoline in human plasma.
authors.affiliation: Bioanalysis and Drugs Analysis Department, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland. Electronic address: joanna.giebultowicz@wum.edu.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Giebułtowicz
authors.affiliation: Department of Cardiology, Grochowski Hospital, Postgraduate Medical School, Warsaw, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Piotrowski
authors.affiliation: Department of Cardiology, Grochowski Hospital, Postgraduate Medical School, Warsaw, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Baran
authors.affiliation: Department of Cardiology, Grochowski Hospital, Postgraduate Medical School, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kułakowski
authors.affiliation: Bioanalysis and Drugs Analysis Department, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wroczyński
mesh_terms: D000328:Adult; D000865:Antazoline / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D006207:Half-Life; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D059625:Liquid-Liquid Extraction / Q000379:methods; D008297:Male; D008698:Mesylates / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D008698:Mesylates; D000865:Antazoline
keywords: Atrial fibrillation; Bioanalysis; Liquid chromatography coupled to mass spectrometry pharmacokinetics