Cloud-point extraction is compatible with liquid chromatography coupled to electrospray ionization mass spectrometry for the determination of bisoprolol in human plasma

Abstract

Cloud-point extraction (CPE) draws increasing interest in a number of analytical fields including bioanalysis, but combining CPE and LC–MS with electrospray ionization (ESI) in the determination of drugs in biological fluids such as plasma, serum or blood has not been reported so far. Bisoprolol was determined in human plasma by CPE using Trition X-114 as a surfactant and metoprolol as the internal standard. NaOH concentration, temperature and Trition X-114 concentration were optimized. All analyses were performed using liquid chromatography–electrospray ionization-tandem mass spectrometry (LC–ESI–MS/MS). All validation experiments met international acceptance criteria and no significant matrix effect was observed. The compatibility of CPE and LC–ESI–MS/MS was confirmed using clinical plasma samples and appropriate statistical tests. The determination of bisoprolol concentration in human plasma in the range 1.0–70ngmL−1 by the CPE method leads to the results which are equivalent to those obtained by the widely used liquid–liquid extraction method. The results revealed that a structural analogue may be an appropriate internal standard when CPE is used as the extraction technique. CPE offers significant practical advantages over the classical extraction methods, including a positive impact on the environment, therefore its wider application in future pharmacokinetic studies is justifiable.