Diagnostic Approach to Disease Using Non-invasive Samples Based on Derivatization and LC-ESI-MS/MS

Abstract

The determination of biologically-active molecules is very important in order to understand biological functions. A novel approach for the highly sensitive and specific determination seems to be essential for this purpose. Based on this consideration, we synthesized various types of fluorogenic and fluorescent reagents for the derivatization of chiral and achiral molecules. The fluorescence analysis is excellent for the analysis of target molecules and generally provides good expected results. However, the trace analysis of the bioactive molecules in complex matrices, such as plasma and urine, is not always satisfactory even using high-performance fluorometry. In such a situation, mass spectrometry (MS) is another technique for the selective and sensitive determination of biological components. Therefore, various derivatization reagents for MS/MS detection were developed and used for the determination of amines and carboxyls including chiral molecules. These newly developed reagents were also adopted for the biomarker detection related to diseases using non-invasive samples (i.e., saliva, nail, hair). Although the determination of the targeted chiral molecules is relatively easy, it is very difficult to identify and/or determine the enantiomeric biomarker in real samples. To solve this difficulty, we proposed the strategy called "chiral metabolomics," which means the total analysis of the enantiomers of various chiral metabolites in complex matrices. This review paper focused on the development of various new derivatization reagents for amines and carboxyls by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and the detection of the biomarker candidates related to several diseases in non-invasive samples (i.e., hair, nail, saliva) using these reagents.

The great importance of normalization of LC–MS data for highly‐accurate non‐targeted metabolomics

“…Analyzing the tagged samples improves the reproducibility of quantitative analyses and ease of peak identification. (Toyo'oka, , ). On the other hand, removing the components that induce matrix effects by solid phase extraction in the pretreatment process and optimizing the LC separation protocol to separate the analyte molecules from the co‐eluting matrices were demonstrated to be beneficial by many researchers.…”

“…Analyzing the tagged samples improves the reproducibility of quantitative analyses and ease of peak identification. (Toyo'oka, 2012(Toyo'oka, , 2016.…”

Derivatization-based High-throughput Bioanalysis by LC-MS

“…The reagents described in the previous sections are useful for the sensitive and specific analysis of amines and carboxylic acids by fluorometry [58][59][60][61][62][63] and MS. [7][8][9][10][11][12][13] However, the determination of each enantiomer of chiral molecules is essentially impossible because there is no chiral recognition moiety in the reagent structures. Therefore, chiral-derivatization reagents for the separation and detection of a pair of enantiomers were also developed in our laboratories (Fig.…”

“…Mass spectrometry (MS) is an alternative technique for the selective and sensitive determination of biological components, [7][8][9][10][11][12][13] the same as fluorescence analysis. MS instrumentation has gradually decreased and the analytical software is also good enough for efficient determinations.…”

The Recent Advances of Fluorescent Sensors Based on Molecularly Imprinted Fluorescent Nanoparticles for Pharmaceutical Analysis

“…However, since few substances possess fluorescence property in nature, the direct fluorescence analysis of the target analytes is relatively seldom applied. Thus, some strategies are taken to render the analytes with fluorescent properties by derivatization [1,2] and dye labeling [3,4] , etc. Recently, a more prevalent way relies on the fluorescent probe, by which the target analytes could be indirectly qualitatively or quantitatively analyzed by fluorescence change of the fluorescent probe.…”