The Detection and Identification of Quaternary Nitrogen Muscle Relaxants in Biological Fluids and Tissues by Ion-Trap LC-ESI-MS

Abstract

Quaternary nitrogen muscle relaxants pancuronium, rocuronium, vecuronium, gallamine, suxamethonium, mivacurium, and atracurium and its metabolites were extracted from whole blood and other biological fluids and tissues by using a solid-phase extraction procedure. The extracts were examined by using high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). The drugs were separated on a ODS column in a gradient of ammonium acetate buffer (pH 5.0) and acetonitrile. Full-scan mass spectra of the compounds showed molecular ions, and MS-MS spectra showed fragments typical of the particular compounds. LC-ESI-MS allowed an unequivocal differentiation of all muscle relaxants involved. The method was applied in a case of rocuronium and suxamethonium administration in a Caesarian section and in a case of intoxication by pancuronium injection. In both cases, the administered drugs could be detected and identified in the supplied samples.

Determination of Vecuronium Bromide in Pharmaceuticals: Development, Validation and Comparative Study of HPLC and CZE Analytical Methods

“…Vecuronium bromide (VB) is a nondepolarizing neuromuscular blocking agent; it is chemically designated as [(2S,3S,5S,8R,9S,10S,13S,14S,16S,17R)-3-Acetyloxy-10, 13-dimethyl-16-(1-methylpiperidin-1-ium-1-yl)-2-piperidin-1-yl-2, 3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl] acetate bromide. VB presents all pharmacological actions of the curare, in addition; this drug interferes in the transmission of neuromuscular end plate and causes diminished central nervous system activity.…”

“…The adjunctive use of neuromuscular blocking drugs makes it possible to achieve an adequate muscle relaxation for all types of surgical procedures without the cardiorespiratory depressant effects of deep anesthesia [1][2][3]. Several analytical methods have been reported for the analysis of VB in biological fluids and pharmaceutical preparations, and these include LC-MS [4][5][6][7][8][9], LC with electrochemical detection [10,11], LC by using solid phase extraction with post-column ion-pair extraction and fluorimetric detection [12], and capillary gas chromatography by using nitrogen sensitive detection [13]. Its final degradation product (3,17-desacetyl vecuronium) is via hydrolysis hence the aim of this research was to develop and validate two simple and reliable analytical methods for the quantitative determination of VB in pharmaceuticals by separating its final degradation product as well as to compare the performance of chromatographic and electrophoretic techniques.…”

Instability of pancuronium in postmortem blood and liver taken after a fatal intramuscular Pavulon injection

“…For determination of pancuronium the method by Kerskes et al [1] was modified and validated. Muscle from the injection site was extracted and an empty ampoule was rinsed twice with methanol.…”

“…Nisikawa et al [6] applied the rapid screening test to nine quaternary ammonium compounds using direct inlet electron impact ionisation mass spectrometry (DI/EI-MS). Kerskes et al [1] used highperformance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) with ion trap source (ITD) for detection and identification of nine compounds from this class of drugs. A capillary electrophoresis (CE) with ultraviolet (UV) detection for separation and detection of quaternary ammonium drugs was also introduced [13].…”

Fall downstairs: accident, homicide or natural death?

“…However, target analyses for the detection of SUX and succinylmonocholine (SMC) according to previously published procedures using thin-layer chromatography [1], GC/MS [1,8,27] and liquid chromatography/mass spectrometry (LC/MS) [2,17,32] revealed negative results.…”