Capillary electrophoresis with dual diode array detection and tandem mass spectrometry to access cardiovascular biomarkers candidates in human urine: Trimethylamine-N-Oxide and L-carnitine

被引：17

作者：

Cieslarova, Zuzana ^{[1
]}

Magaldi, Mariana ^{[2
]}

Barros, Lucelia Alcantara ^{[3
]}

do Lago, Claudimir Lucio ^{[1
]}

Oliveira, Daniel Rossado ^{[1
]}

Helfenstein Fonseca, Francisco Antonio ^{[4
]}

Izar, Maria Cristina ^{[4
]}

Lopes, Aline Soriano ^{[3
]}

Maggi Tavares, Marina Franco ^{[1
]}

Klassen, Aline ^{[3
]}

机构：

[1] Univ Sao Paulo, Inst Chem, Sao Paulo, SP, Brazil

[2] Fed Univ Sao Paulo UNIFESP, Dept Pharmaceut Sci, Diadema, SP, Brazil

[3] Fed Univ Sao Paulo UNIFESP, Dept Chem, Rua Prof Arthur Riedel 275, BR-09972270 Diadema, SP, Brazil

[4] Fed Univ Sao Paulo UNIFESP, Dept Med, Div Cardiol, Sao Paulo, SP, Brazil

来源：

JOURNAL OF CHROMATOGRAPHY A | 2019年 / 1583卷

基金：

巴西圣保罗研究基金会;

关键词：

Cardiovascular biomarkers; Targeted metabolomics; CE-UV-MS/MS; Dual detection; Creatinine; CONTACTLESS CONDUCTIVITY DETECTION; ELECTROCHEMICAL DETECTION; MS/MS METHOD; CE-MS; METABOLOMICS; LIQUID; FLUORESCENCE; VALIDATION; PLASMA; ASSAY;

D O I：

10.1016/j.chroma.2018.10.005

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

A capillary electrophoresis with diode array and tandem mass spectrometry detection (CE-UV-MS/MS) method has been developed for the targeted assessment of cardiovascular biomarkers candidates, trimethylamine-N-Oxide (TMAO) and L-carnitine, and creatinine in human urine samples. The dual detection was applied due to the high concentration of creatinine (monitored by UV detection at 200 nm) in relation to TMAO and t-carnitine (quantified by selected reaction monitoring (SRM) mass spectrometry), in human urine. All instrumental parameters, sheath liquid (SHL) and background electrolyte (BGE) compositions were optimized with a pool of urine provided by adult healthy volunteers and evaluated by signal-to-noise ratio (SNR) and peak shape of TMAO. The compositions for the optimized BGE was formic acid at concentration of 0.10 mol L-1, and for SHL was 70:30 MeOH:H2O containing 0.05% (v/v) formic acid, delivered at a flow rate of 5 mu L min(-1). Limits of detection for TMAO, L-carnitine and creatinine were 0.76, 0.54 and 303 mu mol L-1, respectively. Limits of quantification were 2.5, 1.8 and 1000 mu mol L-1, respectively. Linearity was evaluated by ANOVA and presented R-2 from 0.993 to 0.997. Precision and accuracy were evaluated at three concentration levels. Coefficients of variation (CV) from 1 to 21% were obtained for the intra-day precision evaluation and from 2 to 16% for the inter-day precision evaluation. The recovery ranged from 75 to 116%. Quantitation of TMAO and L-carnitine in infarcted patients urine in comparison to healthy individuals indicated a 2.2 fold increase of TMAO and a 7.0 fold increase of L-carnitine. These results showed the potential applicability of the proposed method for the evaluation of TMAO and L-carnitine in urine within a panel of candidate metabolites in targeted metabolomics studies of cardiovascular diseases among other conditions. (C) 2018 Elsevier B.V. All rights reserved.

引用

页码：136 / 142

页数：7

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