title: Determination of five antiarrhythmic drugs in human plasma by dispersive liquid-liquid microextraction and high-performance liquid chromatography.
abstract: A fast and sensitive high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection was developed and validated for the simultaneous quantitation of five antiarrhythmic drugs (metoprolol, propranolol, carvedilol, diltiazem, and verapamil) in human plasma samples. It involves dispersive liquid-liquid microextraction (DLLME) of the desired drugs from 660 µL plasma and separation using isocratic elution with UV detection at 200 nm. The complete separation of all analytes was achieved within 7 min. Acetonitrile (as disperser solvent) resulting from the protein precipitation procedure was mixed with 100 µL dichloromethane (as an extraction solvent) and rapidly injected into 5 mL aqueous solution (pH 11.5) containing 1% (w/v), NaCl. After centrifugation, the sedimented phase containing enriched analytes was collected and evaporated to dryness. The residue was re-dissolved in 50 µL de-ionized water (acidified to pH 3) and injected into the HPLC system for analysis. Under the optimal conditions, the enrichment factors and extraction recoveries ranged between 4.4-10.8 and 33-82%, respectively. The suggested method was linear (r(2) ≥0.997) over a dynamic range of 0.02-0.80 µg mL(-1) in plasma. The intra- and inter-days relative standard deviation (RSD%) and relative error (RE%) values of the method were below 20%, which shows good precision and accuracy. Finally, this method was applied to the analysis of real plasma samples obtained from the patients treated with these drugs.
authors.affiliation: Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: ajouyban@hotmail.com.
authors.forename: Abolghasem
authors.initials: A
authors.lastname: Jouyban
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran. Electronic address: soruraddin@tabrizu.ac.ir.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Sorouraddin
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran. Electronic address: mafarajzadeh@yahoo.com.
authors.forename: Mir Ali
authors.initials: MA
authors.lastname: Farajzadeh
authors.affiliation: Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Science, Tabriz, Iran. Electronic address: mhosseinsina@yahoo.com.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Somi
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran; Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Science, Tabriz, Iran. Electronic address: rana_fazeli@yahoo.com.
authors.forename: Rana
authors.initials: R
authors.lastname: Fazeli-Bakhtiyari
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005260:Female; D006801:Humans; D059627:Liquid Phase Microextraction; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results
chemical_list: D000889:Anti-Arrhythmia Agents
keywords: Antiarrhythmic drugs; Dispersive liquid–liquid microextraction; High-performance liquid chromatography–ultraviolet; Method validation; Plasma