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Optimization of cloud-point extraction method for determination of bisoprolol in human plasma by LC-MS/MS 

Grzegorz Kojro 1,3Joanna Giebułtowicz 1Ryszard Marszałek 1Katarzyna Buś-Kwaśnik 2Piotr J. Rudzki 2Piotr Wroczyński 1

1. Medical University of Warsaw, Department of Bioanalysis and Drugs Analysis (WUM), Żwirki i Wigury, Warsaw 02-091, Poland
2. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland
3. Valeant sp. z o.o. sp. j., Marynarska 15, Warszawa 02-674, Poland

Abstract

Beta-blockers are a group of pharmaceuticals frequently used in cardiology, in the treatment of arterial hypertension, ischemic heart rhythm disorders and heart failure. One of the most common prescribed and the safest, especially for patients with bronchial diseases and/or diabetes, and peripheral circulatory disorders is bisoprolol.

There are numerous methods of its extraction from serum or plasma, which were used for sample preparation during pharmacokinetic studies. The most popular is solvent extraction method (LLE), because is fast, inexpensive and require only minimal equipment investment. The alternative method possessing all the advantages is an environmental friendly extraction technique - cloud point extraction (CPE). CPE is based on fact that low surfactant concentrations above the critical micelle concentration can exist as homogeneous isotropic liquid phase which separates into two isotropic phases, both of which contain surfactant but which differ in total surfactant concentration. In the surfactant micellar-rich phase any hydrophobic organic components originally present in the sample will be concentrated and separated to other, more hydrophilic under the given conditions compounds. The aim of this work was to create a fast, simple, accurate and environmental friendly method for determination of bisoprolol in plasma using CPE.

CPE was performed using Trition X-114 as a surfactant and metoprolol as internal standard. The optimization of the extraction included testing of various NaOH concentration, temperature and Trition X-114 concentration. The CPE method was compared to previously reported liquid-liquid extraction. The concentration of extracted analyte was determined using the liquid chromatography-electrospray ionisation-tandem mass spectrometer (LC-MS/MS) method operated under the multiple reaction monitoring mode (MRM).

The experimental results suggest that CPE can be an innovative sample preparation method applied for bisoprolol determination in human plasma.

 

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Submitted: 2014-03-15 10:08
Revised:   2014-03-15 16:22