LC-ESI-MS-MS Method for Monitoring Dopamine, Serotonin and Their Metabolites in Brain Tissue

A rapid and precise LC-ESI-MS-MS method for the parallel identification and quantification of dopamine, serotonin and their metabolites (homovanillic acid, 3-methoxytyramine, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolacetic acid) from rat brain tissue without any pre-analysis adjustment of the sample such as pre-concentration or derivatization has been developed. In particular, the reaction-monitoring mode was selected for its extremely high degree of selectivity and the stable-isotope-dilution assay for its high precision of quantification. Alternation the ionization polarity in the course of mass spectrometry detection enabled to determine substances susceptible to various ionization modes in only one analysis run. This fact, in combination with an easy pre-treatment step, constitutes the method straightforward and time undemanding. The developed method was characterized with a high precision (a parts per thousand currency sign19.5%, determined as RSD), an acceptable accuracy (a parts per thousand yen82.0%, determined as recovery), a low limit of detection (a parts per thousand currency sign0.40 ng/100 mg brain tissue) and a low limit of quantification (a parts per thousand currency sign0.42 ng/100 mg brain tissue). The method has been applied in a recent animal study. The levels of the studied neurotransmitters have been determined in the rat brain hippocampus, prefrontal cortex, and striatum in an animal model of schizophrenia induced by an acute dose of a dizocilpine.