Ionic liquid based ultrasound assisted dispersive liquid-liquid micro-extraction for simultaneous determination of 15 neurotransmitters in rat brain, plasma and cell samples

Neurotransmitters are signaling molecules which play a key role in the central nervous system allowing signal transmission in the neuronal synapses. The role of these compounds is very crucial in the biological systems. A rapid, sensitive, economical and derivatisation free method has been developed for the analysis of 15 neurotransmitters in a single run on liquid chromatography tandem mass spectrometry. These 15 neurotransmitters are categorized into 5 groups on the basis of their fragmentation pattern. The proposed method ionic liquid based ultrasound assisted dispersive liquid-liquid microextraction hyphenated with tandem mass spectrometry is the first report for the analysis of neurotransmitters in cell samples along with other two matrices (rat brain and plasma). All the parameters that influence the extraction efficiency are optimized with aid of response surface methodology and desirability profile. Under these optimized conditions the developed method has been validated. The limit of detection was in the range of (1) 0.021-0.912 mu g L-1 for rat brain samples, (2) 0.028-0.978 mu g L-1 for plasma samples and (3) 0.025-0.945 mu g L-1 for cell samples with good linearity behavior for all analytes in the concentration range of 0.04-200 mu g L-1 in all the three matrices. The coefficient of determination for all the neurotransmitters was found in the range of (1) (R-2) >= 0.996 to 0.999 for rat brain samples and (2) (R-2) > 0.991 to 0.999 for plasma and cell samples. The intra-day and inter-day variations were found less than (1) 1.78% and 8.94% for rat brain samples, (2) 1.83% and 8.37% for plasma samples and (3) 1.64% and 8.04% for cell samples respectively. The method has mean recoveries varied between (1) 81-128% for brain samples, (2) 88-107% for plasma samples and (3) 91-104% for cell samples at different spiking levels. The optimized and validated method was found free from matrix interferences and successfully applied for quantitative determination of 15 neurotransmitters in the rat brain, plasma and cell samples. (C) 2018 Elsevier B.V. All rights reserved.