Comparison of hydrodynamically closed two-dimensional capillary electrophoresis coupled with ultraviolet detection and hydrodynamically open capillary electrophoresis hyphenated with mass spectrometry in the bioanalysis of varenicline

Abstract

Two capillary electrophoresis methods for monitoring renally excreted varenicline, a highly effective drug prescribed for smoking cessation, in human urine were developed and compared. A method combining capillary electrophoresis with mass spectrometry was proposed for the fast analysis of varenicline (analysis time up to 7 min). Here, mass spectrometry was a prerequisite for achieving high sensitivity and selectivity of the analysis suitable for the quantification of a 15 ng/mL level of varenicline in un-pretreated urine matrices. An alternative approach, two-dimensional (column-coupled) capillary electrophoresis with enhanced sample load capacity and ultraviolet detection, was proposed as a low-cost alternative to capillary electrophoresis with mass spectrometry. The isotachophoresis on-line sample treatment included simple elimination of the major matrix constituents and stacking of the sample in a large volume so that threefold lower quantitation limits could be easily achieved in comparison to the capillary electrophoresis with mass spectrometry. On the other hand, longer analysis time (ca. 4.5-fold) and more complex electrolyte system in the coupled zone electrophoresis step (including two additives enhancing separation selectivity, i.e. isopropanol and cyclodextrin) were prerequisites for the complete separation of varenicline from the sample matrix. Anyway, both the developed methods were validated according to the Food and Drug Administration guidelines showing favorable performance parameters, suitable for their routine biomedical use.

Recent progress in analytical capillary isotachophoresis

“…Piešťanský and co‐workers developed two methods for monitoring varenicline in human urine, a drug prescribed for smoking cessation. The results of CZE with MS detection (BGE: 20 mM HAc) were compared with online ITP‐CZE with UV detection at 237 nm (LE: 10 mM NH 4 Ac, 20 mM MES, 0.1% methyl 2‐hydroxyethyl cellulose (MHEC), pH 5.56; TE: 10 mM EACA, 10 mM HAc, 0.1% MHEC, pH 4.55; BGE: 25 mM EACA, 50 mM HAc, 10 mM 2‐hydroxypropyl)‐β‐cyclodextrin, 20% isopropyl alcohol, 0.1% MHEC, pH 4.62).…”

“…Piešťanský and co-workers [54] developed two methods for monitoring varenicline in human urine, a drug prescribed for smoking cessation. The results of CZE with MS detection (BGE: 20 mM HAc) were compared with online ITP-CZE with UV detection at 237 nm (LE: 10 mM NH 4 Ac, 20 mM MES, Both techniques proved to be suitable for routine urine analyses, providing LODs of 10 and 3.0 g/L, respectively (see Fig.…”

Recent advances in CE and microchip‐CE in clinical applications: 2014 to mid‐2017

“…CE‐MS is becoming popular for drug and metabolite analysis. There have been some reports of successful analyses performed using CE in combination with different MS instruments such as the detection of pheniramine and its metabolite phenylephrine in urine using either hydrodynamically closed ITP‐CE or open capillary CE‐tandem MS , Varenicline in urine by 2D CE‐UV or open capillary CE‐MS , and morphine and its isobaric glucuronide metabolites by CE‐ESI‐QTOF‐MS .…”

Capillary electrophoresis for the investigation of two novel aminoalkanol derivatives of 1,7‐diethyl‐8,9‐diphenyl‐4‐azatricyclo[5.2.1.02,6] dec‐8‐ene‐3,5,10‐trione as potential anticancer drugs in water solution and serum

“…The advantages of CE include its simplicity, high efficiency, versatility, speed, high‐resolution power, small sample volume required, and low operating costs, as well as ability to analyze a diverse spectrum of analytes ranging from small organic ions to macromolecular protein complexes or DNA . CE is an analytical technique with an increasing role in biological, pharmacological, drug discovery, and clinical research . It seems to be the most commonly used technique that provides very good results in analyses of various substances, including active pharmaceutical ingredients .…”