Abstract
The study focused on the application of high-resolution mass spectrometry (HRMS) to postmortem toxicological analysis. Fast and simple sample preparation involved precipitation with acetonitrile, removal of phospholipids using special columns and filtration. Qualitative and quantitative analyses were performed using ultra-performance liquid chromatography coupled with quadrupole time-of–flight mass spectrometry. The method was validated by determining the limit of quantification, precision, recovery and matrix effect. The use of a high-resolution spectrometer allowed us to determine the precise masses of the fragments of interest and to suggest the fragmentation pathway of baclofen. The usefulness, effectiveness and assets of the procedure were confirmed by an authentic case of a 25-year-old woman fatally intoxicated with baclofen who was found dead in her apartment. Toxicological analysis of postmortem blood samples demonstrated that the baclofen concentration was 30.7 μg/mL. In only one published case describing fatal baclofen intoxication were no other xenobiotics (that could interact with baclofen) found. To our knowledge, this is the first report dealing with analysis of baclofen by HRMS.
Highlights
Baclofen [(±)-4-amino-3-(4-chlorophenyl) butanoic acid, b-(aminomethyl)-4-chlorobenzenpropane acid, Fig. 1], with commercial names of AtrofenÒ, BaclofenÒ, LioresalÒ and LyflexÒ
It can be assumed that the concentration at 0.5 lg/mL of baclofen in blood was a limit of detection (LOD)
The study findings demonstrate that the specific, simple and quick procedure described by us for determination of baclofen in autopsy blood can be successfully used for routine toxicology testing in the cases of suspected baclofen intoxication
Summary
Baclofen [(±)-4-amino-3-(4-chlorophenyl) butanoic acid, b-(aminomethyl)-4-chlorobenzenpropane acid, Fig. 1], with commercial names of AtrofenÒ, BaclofenÒ, LioresalÒ and LyflexÒ. Baclofen is a drug affecting the central nervous system (CNS). The mechanism of action of baclofen, which is a derivative of c-aminobutyric acid (GABA), involves stimulation of GABAB-ergic receptors located pre- and postsynaptically [1]. The substance decreases the skeletal muscle tone by inhibiting the mono- and polysynaptic reflexes at the spinal cord level, but does not affect the neuromuscular conduction [2]. Baclofen is used for the treatment of spinal cord diseases, cerebral stroke and cerebrospinal meningitis. It is applied in patients with severe chronic spasticity in multiple sclerosis [3, 4]. The drug is known to minimize the symptoms of alcohol craving [5,6,7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
