Current trends in isotope‐coded derivatization liquid chromatographic‐mass spectrometric analyses with special emphasis on their biomedical application

Abstract

Currently, LC–MS has various applications in different areas such as metabolomics, pharmacokinetics, and pathological studies. Yet, matrix effects resulting from co‐existing constituents remain a major problem for LC–MS [or LC–tandem mass spectrometry (LC–MS/MS)]. Moreover, technical problems and instrumental drifts may lead to ion abundance variance. Thus, an internal standard (IS) is required to guarantee the accuracy and precision of the method. Because of their limited number, isotope‐coded derivatization (ICD) has been recently introduced to overcome this problem. For ICD, a stable heavy isotope‐coded moiety is used for labeling the standard or the control sample and the formed products can act as ISs. A light form of the reagent is used for labeling the sample. Then, both are mixed and analyzed by LC–MS(/MS). This strategy permits the identification of different unknown analytes including potential metabolites and disease biomarkers. All these attributes lead to persistent growth in the applications of ICD LC–MS(/MS) in various biomedical branches. In this article we review the ICD methods published in the last eight years for biomedical applications as well as briefly summarize other applications for environmental and food analyses as some of their used ICD reagents were further applied for analyzing biological specimens or have the potential for that.

Metabolic Profiling of Urinary Chiral Amino-Containing Biomarkers for Gastric Cancer Using a Sensitive Chiral Chlorine-Labeled Probe by HPLC-MS/MS

“…The collision-induced dissociation (CID) fragmentation of the D-BPCl-labeled diastereomeric derivatives of D, L-amino acids was illuminated using high-resolution mass spectrometry. A common product ion at m/z 218 with a high abundance from both the precursor ions [M − H] − for 35 Cl and [M + 2-H] − for 37 Cl could be observed, as shown in Figure 1B,C S2) for our analysis, and the [M − H] − → 218 transition was used for quantitative analysis due to its peak area being about three times greater than that of the [M + 2-H] − → 218 transition. In addition, a common product ion at m/z 105 shown in the positive ion mode (Scheme S1) was also used for pseudotargeted analysis.…”

“…32,33 To address these issues, an indirect analytical method by derivatization reagents 34 has been developed and used in the clinic 35 based on LC−MS, GC− MS, and CE-MS. 36 Among them, chemical isotope labeling (CIL) in combination with LC−MS has emerged as a remarkable strategy in analysis of chiral amino-containing compounds. 35 Several CIL reagents such as (S)-COXA-OSu and (S)-COXA-d 5 -OSu, 37 16 O 2 -/ 18 O 2 -based CIL reagents, 38 12 C 2 -/ 13 C 2 -MBAA-NHS, 12 C 2 -/ 13 C 2 -DBAA-NHS, 39 DMAP, and d 4 -DMAP, 40 have been developed for the labeling of amino-containing metabolites. Another stable isotope labeling reagent example is the duplex mass defect-based N,N-dimethyl leucine (mdDiLeu) reagents, which have a mass difference of 20.5 mDa between the two DiLeu isotopologues, and they were applied to the quantitative analysis of proteins and amine metabolites in pancreatic cancer cells.…”

“…Moreover, many amino acids have the characteristics of high polarity and lack of chromophores, which increases the difficulty of analysis on conventional C18 columns. Direct chiral column analysis is a good choice to resolve these enantiomers, but the price is somewhat expensive for large-scale analysis. , To address these issues, an indirect analytical method by derivatization reagents has been developed and used in the clinic based on LC–MS, GC–MS, and CE-MS . Among them, chemical isotope labeling (CIL) in combination with LC–MS has emerged as a remarkable strategy in analysis of chiral amino-containing compounds .…”

Derivatization procedures and their analytical performances for HPLC determination in bioanalysis

“…Isotope‐labeling derivatization (ILD) uses derivatization reagents that are labeled by replacing specific atoms by their isotope. The result of derivatization is an isotopic‐labeled derivative that shifts its mass relative to a nonlabeled derivative for the identification purposes in bioanalysis by HPLC–MS, but compensation of matrix effects is also considered (El‐Maghrabey, Kishikawa, & Kuroda, 2020; Srinivas, 2009). The ILD method can improve chromatographic sensitivity, but also solves the problem of unavailability of isotope internal standards in bioanalysis by HPLC–MS (He, Luo, Chen, Hou, & Hu, 2017).…”

Progress and Challenges in Quantifying Carbonyl-Metabolomic Phenomes with LC-MS/MS

“…Several excellent reviews have focused on isotope-coded derivatization strategies and their applications in global metabolomics or targeted small-molecular weight compounds [39][40][41][42][43]. In this review, we focus on the detection of carbonyl-containing metabolites and present the general principles and properties of representative derivatization reagents, as well as their advantages and shortcomings.…”