Identification and quantitation of six non-depolarizing neuromuscular blocking agents by LC-MS in biological fluids.

A liquid chromatography-electrospray-mass spectrometry technique for the screening and determination of five non-depolarizing neuromuscular blocking agents (NDBAs), atracurium and its product of degradation/metabolite laudanosine, rocuronium, pancuronium, vecuronium, and mivacurium has been developed using ambenonium as the internal standard (I.S.). Samples were acidified upon reception by adding 20 micro L 0.5M H(2)SO(4) to 500 micro L of biofluid. Sample preparation consisted of simple blood purification and/or protein precipitation using 1 mL I.S. in acetonitrile. Chromatographic separation was carried out on an X-TERRA trade mark column along with a gradient of acetonitrile in 2mM ammonium formate (pH 3). Detection was carried out in the positive selected ion monitoring mode, targeting one quantitation ion and one confirmation ion per compound. The limit of quantitation was 2.5 micro g/L for mivacurium and laudanosine, 5 micro g/L for rocuronium and pancuronium and 10 micro g/L for atracurium and vecuronium in serum (i.e., in the range of, or less than, therapeutic levels). The technique was found to be linear between the respective LOQs and 2000 micro g/L, with correlation coefficients higher than 0.999 in all matrices. Intra- and interday precision and accuracy in serum fulfilled the international criteria. This method was employed for the investigation of a case of suicide by infusion of drugs. Laudanosine, the metabolite or degradation product of both atracurium and cisatracurium, and rocuronium were found in urine and whole blood, at supratherapeutic concentrations in the latter (rocuronium: 1.53 and 2.18 mg/L, laudanosine: 8.86 and 0.31 mg/L, respectively), and even therapeutic concentrations would have been lethal in the absence of respiratory assistance.

Analytical aspects of volatile substance abuse (VSA).

Through a case report, the authors illustrate the volatile substance abuse (VSA) toxicological investigation difficulties mainly due to evaporation of the compounds from postmortem samples and to the lack of reference data for interpretation. A 17-year-old man, student in a chemistry institute, was found dead with a plastic bag placed over his head. Several chemical substances were found in his belongings. Autopsy findings included serious pulmonary lesions and hemorrhagic digestive ulcerations. A large screening of drugs and toxic compounds and selective analyses for several classes of drugs of abuse were carried out in the autopsy samples. In particular, a headspace (HS), -gas chromatography/-mass spectrometry (GC/MS) technique was used to screen for volatile substances and metabolites in the biological samples and for residues of volatile substances on the surface of the plastic bag and in the chemicals found on the scene. The main analytical finding was the presence of alkanes (heptane, methyl-2-pentane, methyl-3-hexane, methylcyclohexane) in the gastric content. The literature data, VSA practices, long time-delay between death and autopsy, preservation conditions of the biological samples before analysis, and in-lab experiments on evaporation of volatile substances were considered to interpret this result. The present fatality was attributed to VSA with a gasoline-based stain remover like "eau écarlate," associated with a hypoxic recreation practice using a plastic bag.