title: Analysis of amino acid and monoamine neurotransmitters and their metabolites in rat urine of Alzheimer's disease using in situ ultrasound-assisted derivatization dispersive liquid-liquid microextraction with UHPLC-MS/MS.
abstract: Neurotransmitters (NTs) may play an important role in neurodegenerative disorders such as Alzheimer's disease (AD). In order to investigate the potential links, a new simple, fast, accurate and sensitive analytical method, based on in situ ultrasound-assisted derivatization dispersive liquid-liquid microextraction (in situ UA-DDLLME) coupled with ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), has been developed and validated. The quantitation of amino acid neurotransmitters (AANTs) and monoamine neurotransmitters (MANTs) in urine of AD rats were performed in this work. The in situ UA-DDLLME procedure involved the rapid injection of the mixture of low toxic 4-bromoanisole (extractant) and acetonitrile (dispersant), which containing the new designed and synthesized 4'-carbonyl chloride rosamine (CCR) as derivatization reagent, into the aqueous phase of real sample and buffer. Under the selected conditions, the derivatization and microextraction of analytes were simultaneously completed within 1min. Good linearity for each analyte (R>0.992) was observed with low limit of detections (LODs, S/N>3). Moreover, the proposed method was compared with direct detection or other reported methods, and the results showed that low matrix effects and good recoveries results were obtained in this work. Taken together, in situ UA-DDLLME coupled with UHPLC-MS/MS analysis was demonstrated to be a good method for sensitive, accurate and simultaneous monitoring of AANTs and MANTs. This method would be expected to be highly useful in AD diseases' clinical diagnostics and may have potential value in monitoring the efficacy of treatment.
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China. Electronic address: xianenzhao@163.com.
authors.forename: Xian-En
authors.initials: XE
authors.lastname: Zhao
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Yongrui
authors.initials: Y
authors.lastname: He
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: Key Laboratory of TCM Quality Control Technology, Shandong Analysis and Test Center, Shandong Academy of Sciences, 19 Keyuan Street, Jinan 250014, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Tibetan Medicine Research & Qinghai Key Laboratory of Qinghai-Tibet Plateau Biological Resources, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining 810001, Qinghai, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Shandong Provincial Key Laboratory of Life-Organic Analysis & Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, Shandong, PR China.
authors.forename: Jinmao
authors.initials: J
authors.lastname: You
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000652:urine*; D000596:Amino Acids / Q000378:metabolism / Q000652:urine*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D059627:Liquid Phase Microextraction / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000652:urine*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000069453:Ultrasonic Waves
chemical_list: D000596:Amino Acids; D015306:Biogenic Monoamines; D018377:Neurotransmitter Agents
keywords: Alzheimer’s diseases; In situ derivatization; Neurotransmitter; UHPLC–MS/MS; Ultrasound-assisted dispersive liquid-liquid microextraction; Urine