Analysis of Intact Glucuronides and Sulfates of Serotonin, Dopamine, and Their Phase I Metabolites in Rat Brain Microdialysates by Liquid Chromatography-Tandem Mass Spectrometry

被引：66

作者：

Uutela, Paivi ^{[1
]}

Reinila, Ruut ^{[1
]}

Harju, Kirsi ^{[1
]}

Piepponen, Petteri ^{[2
]}

Ketola, Raimo A. ^{[3
]}

Kostiainen, Risto ^{[1
]}

机构：

[1] Univ Helsinki, Fac Pharm, Div Pharmaceut Chem, FI-00014 Helsinki, Finland

[2] Univ Helsinki, Fac Pharm, Div Pharmacol & Toxicol, FI-00014 Helsinki, Finland

[3] Univ Helsinki, Fac Pharm, CDR, FI-00014 Helsinki, Finland

来源：

ANALYTICAL CHEMISTRY | 2009年 / 81卷 / 20期

基金：

芬兰科学院;

关键词：

UDP-GLUCURONOSYLTRANSFERASES; DIHYDROXYPHENYLACETIC ACID; CEREBROSPINAL-FLUID; HUMAN LIVER; 5-HYDROXYTRYPTAMINE; CATECHOLAMINES; IDENTIFICATION; SUPERFAMILY; CONJUGATION; EXPRESSION;

D O I：

10.1021/ac901320z

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

A method for the analysis of intact glucuronides and sulfates of common neurotransmitters serotonin (5-HT) and dopamine (DA) as well as of 5-hydroxy-3-indoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in rat brain microdialysates by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. Enzyme-assisted synthesis using rat liver microsomes as a biocatalyst was employed for the production of 5-HT-, 5-HIAA-, DOPAC-, and HVA-glucuronides for reference compounds. The sulfate conjugates were synthesized either chemically or enzymatically using a rat liver S9 fraction. The LC-MS/MS method was validated by determining the limit,; of detection and quantitation, linearity, and repeatability for the quantitative analysis of 5-HT and DA and their glucuronides, as well as of 5-HLAA, DOPAC, and HVA and their sulfate-conjugates. In this study, 5-HT-glucuronide was for the first time detected in rat brain. The concentration of 5-HT-glucuronide (1.0-1.7 nM) was up to 2.5 times higher than that of free 5-HT (0.4-2.1 nM) in rat brain microdialysates, whereas the concentration of DA-glucuronide (1.0-1.4 nM) was at the same level or lower than the free DA (1.2-2.4 nM). The acidic metabolites of neurotransmitters, 5-HLAA, HVA, and DOPAC, were found in free and sulfated form, whereas their glucuronidation was not observed.

引用

页码：8417 / 8425

页数：9

共 33 条

[11] CONJUGATED 3,4 DIHYDROXY PHENYL ACETIC-ACID (DOPAC) IN HUMAN AND MONKEY CEREBROSPINAL-FLUID AND RAT-BRAIN AND EFFECTS OF PROBENECID TREATMENT [J].

GORDON, EK ;

MARKEY, SP ;

SHERMAN, RL ;

KOPIN, IJ .

LIFE SCIENCES, 1976, 18 (11) :1285-1292

[12] PRESENCE OF CONJUGATED 5-HYDROXYTRYPTAMINE IN INVIVO SUPERFUSATES OF RAT SPINAL-CORD [J].

HAMMOND, DL ;

YAKSH, TL ;

TYCE, GM .

JOURNAL OF NEUROCHEMISTRY, 1981, 37 (04) :1068-1071

[13] Neurotransmission and neurotoxicity by nitric oxide, catecholamines, and glutamate: Unifying themes of reactive oxygen species and electron transfer [J].

Jacintho, JD ;

Kovacic, P .

CURRENT MEDICINAL CHEMISTRY, 2003, 10 (24) :2693-2703

[14] NMR spectroscopic studies on the in vitro acyl glucuronide migration kinetics of lbuprofen ((±)-(R,S)-2-(4-Isobutylphenyl) propanoic acid), its metabolites, and analogues [J].

Johnson, Caroline H. ;

Wilson, Ian D. ;

Harding, John R. ;

Stachulski, Andrew V. ;

Iddon, Lisa ;

Nicholson, Jeremy K. ;

Lindon, John C. .

ANALYTICAL CHEMISTRY, 2007, 79 (22) :8720-8727

[15] Discovery of neurosteroid glucuronides in mouse brain [J].

Kallonen, Sirkku E. ;

Tammimaki, Anne ;

Piepponen, Petteri ;

Raattamaa, Helena ;

Ketola, Raimo A. ;

Kostiainen, Risto .

ANALYTICA CHIMICA ACTA, 2009, 651 (01) :69-74

[16] Expression of UDP-glucuronosyltransferases (UGTs) 2B7 and 1A6 in the human brain and identification of 5-hydroxytryptamine as a substrate [J].

King, CD ;

Rios, GR ;

Assouline, JA ;

Tephly, TR .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1999, 365 (01) :156-162

[17] FAILURE TO DETECT 5-HYDROXYTRYPTAMINE-O-SULPHATE IN NORMAL RAT BRAIN AND AFTER MONOAMINE OXIDASE INHIBITION [J].

KORF, J ;

SEBENS, JB .

JOURNAL OF NEUROCHEMISTRY, 1970, 17 (03) :447-&

[18] Serotonin (5-hydroxytryptamine) glucuronidation in vitro:: assay development, human liver microsome activities and species differences [J].

Krishnaswamy, S ;

Duan, SX ;

Von Moltke, LL ;

Greenblatt, DJ ;

Sudmeier, JL ;

Bachovchin, WW ;

Court, MH .

XENOBIOTICA, 2003, 33 (02) :169-180

[19] Characterization of 1-hydroxypyrene as a novel marker substrate of 3-methylcholanthrene-inducible phenol UDP-glucuronosyltransferase(s) [J].

Luukkanen, L ;

Elovaara, E ;

Lautala, P ;

Taskinen, J ;

Vainio, H .

PHARMACOLOGY & TOXICOLOGY, 1997, 80 (03) :152-158

[20] Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily [J].

Mackenzie, PI ;

Bock, KW ;

Burchell, B ;

Guillemette, C ;

Ikushiro, S ;

Iyanagi, T ;

Miners, JO ;

Owens, IS ;

Nebert, DW .

PHARMACOGENETICS AND GENOMICS, 2005, 15 (10) :677-685

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