Mass Spectrometric and Contactless Conductivity Detection Approaches in the Determination of Muscle Relaxants by Capillary Electrophoresis

Abstract

Novel and rapid capillary electrophoresis-coupled tandem mass spectrometry (CE-MS/MS) and capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C⁴D) methods have been developed for the separation and determination of three neuromuscular blocking agents: pancuronium, vecuronium, and rocuronium. In both cases, the separation was conducted in background electrolytes based on acidic acetate-ammonium buffers to avoid possible decomposition of the analytes that are known to be unstable in alkaline media. Baseline resolution of the analytes was achieved in the presence of modified γ-cyclodextrin by CE with C⁴D detection. The two detection techniques were compared with regard to analytical figures of merit including linear dynamic range, limit of detection, limit of quantification, precision, and accuracy. The calibration curves showed good linearity for both detection methods examined (characterized by r² ≥ 0.9908). The LODs of the CE-MS/MS and the CE-C⁴D methods differed at least by two orders of magnitude considering all analytes. The differences in precision and accuracy of these methods were evaluated and discussed. The assays of pancuronium, vecuronium, and rocuronium in commercial injection solutions by CE-MS/MS and CE-C⁴D were performed and the results compared.

Keywords:

• Capacitively coupled contactless conductivity detection
• CE-ESI-MS
• Muscle relaxants
• Pancuronium
• Rocuronium
• Vecuronium

Acknowledgments

The publication is cofinanced by the European Social Fund and the state budget of the Czech Republic, Project no. CZ.1.07/2.3.00/30.0061. The financial support of the Charles University in Prague - project SVV 267 002 is also gratefully acknowledged.

Notes

*fragment ions used for quantification.

^a Equation of the calibration curve was expressed as y = ac +q where y stands for the peak area (CE-C⁴D – ratio of the corrected peak area of the analyte and the corrected peak area of the IS; CE-MS/MS – uncorrected peak area of the analyte), c is the concentration of the analyte (µg/ml), q is the intercept value, and a is the slope.

^a CE-C⁴D – ratio of the corrected peak area of the analyte and the corrected peak area of the IS.

CE-MS/MS – uncorrected peak area of the analyte.

^a Background concentration of the analyte in the original test solution was approximately 100 µg/ml.

^b Mean of the results of three experiments.

^a Mean of six independent determinations.