A Simple and Sensitive Imidazolium-Based Ionic Liquid-Modified Reversed-Phase Liquid Chromatography Method for the Simultaneous Determination of Beta-Blockers in Human Plasma Samples

Abstract

Beta-blockers (β-blockers) are broadly used to manage cardiac arrhythmia, which could increase in the upcoming years due to the aging population and the increase in the number of patients with cardiac burden. In the current work, a simple, sensitive, and reliable simultaneous determination of five β-blockers (acebutolol, pindolol, atenolol, nadolol, and oxprenolol) was accomplished by ionic liquid (IL)-modified reversed-phase liquid chromatography with ultraviolet detection. The chromatographic separation was achieved on a ZORBAX^® SB-C18 column using a hybrid mobile phase consisting of 50 µg/mL 1-butyl-3-methylimidazolium chloride dissolved in 0.02 mol/L phosphate buffer (pH 3.5) and acetonitrile (70 : 30, v/v). The chromatographic measurements were performed by isocratic elution at a 1.0 mL/min flow rate, 230 nm wavelength, and 25°C column temperature. The current method was applied to human plasma matrices by direct injection of samples with a short analysis time of 12 min. Good linearity was achieved in the range of 3–500 ng/L for atenolol, acebutolol, and pindolol, 7–500 ng/L for acebutolol, and 10–500 ng/L for oxprenolol with a 0.999 coefficient of determination. The limit of detection/limit of quantification values were 1.04/3.00, 2.75/7.00, 1.03/3.00, 1.05/3.00, and 3.47/10.00 ng/L for atenolol, nadolol, acebutolol, pindolol, and oxprenolol, respectively. Results of intra-day and inter-day precision were found to be less than 2%. The sensitivity enhancement factors of analytes due to the addition of IL ranged between 9- and 41-fold higher than that achieved in the absence of IL. Therefore, the proposed method could be used as a simple and sensitive analytical method for routine clinical analysis of β-blockers with the presence of a small amount of IL.