Published: Journal of Analytical Toxicology, ISSN 0146-4760, Volume 31, Number 2, March 2007, pp.75-80

Validation of a Procedure for the Gas Chromatography–Mass Spectrometry Analysis of Cocaine and Metabolites in Pericardial Fluid
María Teresa Contreras[1,2], Marisa González[1], Susana González[1,2], Rosa Ventura[1,3], Juan Luis Valverde[2], Antonio F. Hernández[4], Antonio Pla[4], Albert Vingut[2], Jordi Segura[1,3], and Rafael de la Torre[1,3]
[1]Pharmacology Research Unit, Institut Municipal d’Investigació Mèdica (IMIM);
[2]Department of Barcelona, National Institute of Toxicology, Barcelona;
[3]Universitat Pompeu Fabra (CEXS-UPF); and
[4]Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain

A rapid and sensitive assay for pyridinium oximes in plasma and tissue was developed. The method was suitable for the analysis of mono- and di-pyridinium oximes and utilizes ultrafiltration followed by cation-exchange high-performance liquid chromatography with UV detection. The assay was originally developed for the measurement of the oxime MMB-4 in plasma for which the lower limit of detection was 0.0005 µg and the limit of quantitation was 0.001 to 2.5 µg. The assay required as little as 50 µL of whole blood or 30 µL of tissue homogenate, and it was used for a pharmacokinetic study from a single intramuscular injection of MMB-4 (dichloride or dimethylsulfonate salt) in the guinea pig. Both salts were found to have similar pharmacokinetic properties in the plasma with a T? of about 34 to 42 min and the area-under-the-curve values increased dose dependently. MMB-4 tissue concentrations were much lower than the plasma. The tissue levels peaked at 5–20 min depending on the tissue. A rank of concentration was diaphragm > heart > thigh muscle.

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