Sensitive and accurate determination of neurotransmitters from in vivo rat brain microdialysate of Parkinson's disease using in situ ultrasound-assisted derivatization dispersive liquid–liquid microextraction by UHPLC-MS/MS

A simple, rapid, sensitive and environmentally friendly ultrasound-assisted in situ derivatization dispersive liquid-liquid microextraction (in situ UA-DDLLME) method followed by ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has been developed for the simultaneous determination of amino acid neurotransmitters (AANTs) and monoamine neurotransmitters (MANTs) in rat brain microdialysates and baicalein in blood microdialysates of Parkinson's disease (PD) rats with in vivo multiple sites microdialysis in this work. A novel MS sensitive derivatization reagent 4'-carbonyl chloride rosamine (CCR) with a permanent positive charged moiety, has been designed, synthesized and reported for simultaneous labelling of amino and hydroxyl groups in neurotransmitters. Under the selected conditions, the derivatization and microextraction of analytes were simultaneously completed within 1.0 min. Good linearity for each analyte (R > 0.992) was observed with a low limit of detection (LOD, S/N > 3). Taken together, in situ UA-DDLLME coupled with UHPLC-MS/MS analysis was demonstrated to be a promising method for sensitive, accurate and simultaneous monitoring of AANTs and MANTs in rat brain and baicalein in rat blood. This method would be expected to be highly useful in PD clinical diagnostics and monitoring the efficacy of treatments.