scholarly journals Bioanalytical and Mass Spectrometric Methods for Aldehyde Profiling in Biological Fluids

Toxics ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 32 ◽  
Author(s):  
Romel P. Dator ◽  
Morwena J. Solivio ◽  
Peter W. Villalta ◽  
Silvia Balbo

Human exposure to aldehydes is implicated in multiple diseases including diabetes, cardiovascular diseases, neurodegenerative disorders (i.e., Alzheimer’s and Parkinson’s Diseases), and cancer. Because these compounds are strong electrophiles, they can react with nucleophilic sites in DNA and proteins to form reversible and irreversible modifications. These modifications, if not eliminated or repaired, can lead to alteration in cellular homeostasis, cell death and ultimately contribute to disease pathogenesis. This review provides an overview of the current knowledge of the methods and applications of aldehyde exposure measurements, with a particular focus on bioanalytical and mass spectrometric techniques, including recent advances in mass spectrometry (MS)-based profiling methods for identifying potential biomarkers of aldehyde exposure. We discuss the various derivatization reagents used to capture small polar aldehydes and methods to quantify these compounds in biological matrices. In addition, we present emerging mass spectrometry-based methods, which use high-resolution accurate mass (HR/AM) analysis for characterizing carbonyl compounds and their potential applications in molecular epidemiology studies. With the availability of diverse bioanalytical methods presented here including simple and rapid techniques allowing remote monitoring of aldehydes, real-time imaging of aldehydic load in cells, advances in MS instrumentation, high performance chromatographic separation, and improved bioinformatics tools, the data acquired enable increased sensitivity for identifying specific aldehydes and new biomarkers of aldehyde exposure. Finally, the combination of these techniques with exciting new methods for single cell analysis provides the potential for detection and profiling of aldehydes at a cellular level, opening up the opportunity to minutely dissect their roles and biological consequences in cellular metabolism and diseases pathogenesis.

1982 ◽  
Vol 65 (6) ◽  
pp. 1388-1394 ◽  
Author(s):  
Roger C Snyder ◽  
William C Brumley ◽  
Charles V Breder ◽  
Thomas Fazio

Abstract The confirmation of 2,4- and 2,6-toluenediamine (TDA) in aqueous extracts from boil-in-bags and retortable pouches is described. The extracts were initially analyzed by a high performance liquid chromatographic procedure and any apparent 2,4- and/or 2,6-TDA were quantitated. The liquid chromatographic effluent corresponding to any apparent 2,4- or 2,6-TDA was collected. TDA was then partitioned into ethyl acetate and reacted with trifluoroacetic anhydride (TFAA). The TDA-TFAA derivative formed was confirmed by gas-liquid chromatography (GLC) using a 1.2 m × 0.32 cm nickel column packed with 6% OV-17 on Superpak-20M. Results obtained from analyzing extracts of several retortable pouches and boil-in-bags showed levels of TDA migration ranging from <0.1 to 2.2 ppb (μg/L). Additional confirmation of the TDA-TFAA derivative from retortable pouches by multiple ion detection GC/mass spectrometry is also described.


2019 ◽  
Vol 8 (2) ◽  
pp. 115-120
Author(s):  
I. I. Miroshnichenko ◽  
Y. E. Shilov

Introduction. In the present publication highlights the key points of the main stages of development of methods for determining trace amounts of drugs and metabolites in biological samples using chromatographic and chromatography-mass spectrometry methods. The main sources of errors are specified. The main attention is paid to chromatography-mass spectrometry, which is the basic method of analysis of small molecules in biological samples. Examples from literary sources and authors' own practice are given.Text. The review highlights some of the practical issues of preparation of calibration samples, method of increasing the stability of the sample at the stage of sampling and plasma preparation. In particular, the influence of various anticoagulants on the accuracy of the analysis is reflected. Specify the method of reducing back conversion of some metabolites of carboxyl-containing drugs to parent compound to prevent overestimation of the results of quantitative determination. Some methods of sample preparation, which have become widespread recently, are noted. For example, solid supported liquid-liquid extraction, based on the extraction of the component of interest from the water sample into the liquid layer distributed on a solid high-polar carrier, followed by eluting by a system of non-polar solvents that do not mix with this layer. Recommendations on the use of internal standards, the preparation of the mobile phase for HPLC, on chromatographic separation, validation techniques are given. In the section «Mass spectrometric detection» features of preparation of a mobile phase for chromatography-mass spectrometry experiments are given. The questions of carry-over reduction, ion suppression, matrix effect are covered. The phenomenon of cross-talk in the study of drug metabolism by chromatography-mass spectrometry is discussed. It consists in the mutual distortion of the mass spectrometric response, when the same mass fragments are formed from different ions-precursors. Features of development of techniques for high-performance pharmacokinetic screening are given.Conclusion. The authors hope that the presented material will be useful for scientists and specialists in the field of pharmacokinetics, biomarker discovery and clinical analyses.


2022 ◽  
Vol 23 (2) ◽  
pp. 693
Author(s):  
Mirela Sarbu ◽  
Raluca Ica ◽  
Alina D. Zamfir

Gangliosides are effective biochemical markers of brain pathologies, being also in the focus of research as potential therapeutic targets. Accurate brain ganglioside mapping is an essential requirement for correlating the specificity of their composition with a certain pathological state and establishing a well-defined set of biomarkers. Among all bioanalytical methods conceived for this purpose, mass spectrometry (MS) has developed into one of the most valuable, due to the wealth and consistency of structural information provided. In this context, the present article reviews the achievements of MS in discovery and structural analysis of gangliosides associated with severe brain pathologies. The first part is dedicated to the contributions of MS in the assessment of ganglioside composition and role in the specific neurodegenerative disorders: Alzheimer’s and Parkinson’s diseases. A large subsequent section is devoted to cephalic disorders (CD), with an emphasis on the MS of gangliosides in anencephaly, the most common and severe disease in the CD spectrum. The last part is focused on the major accomplishments of MS-based methods in the discovery of ganglioside species, which are associated with primary and secondary brain tumors and may either facilitate an early diagnosis or represent target molecules for immunotherapy oriented against brain cancers.


2008 ◽  
Vol 27 (2) ◽  
pp. 99
Author(s):  
Dobrin Nedelkov

Current emphasis on discovering and correlating human genetic variations lays the foundation for future studies of human protein diversity. Protein posttranslational processing, along with the translation of genetic variations, results in a complex, variable human proteome. Analyzing these protein variations on a grandeur scale has become feasible with the advent of mass spectrometry. Mass spectrometry is the only detection method today that can universally provide information about specific protein structural modifications, without a priori knowledge of the modification. However, high-throughput separation approaches are needed to effectively prepare the proteins for mass spectrometric interrogation. Such are the immunoaffinity separations that target single proteins by using highly specific antibodies for their affinity retrieval from the biological fluids. The resulting combination of immunoaffinity separation with MALDI-TOF mass spectrometry, termed Mass Spectrometric Immunoassay (MSIA), has been recently applied in two large studies of protein diversity. The results of these studies reveal a human protein diversity that is far more complex than the variations observed at the genetic level. Assessing the human proteome variations among and within populations will be an important future undertaking with significant clinical and diagnostic implications.


Author(s):  
Sylvain Lehmann ◽  
Pauline Poinot ◽  
Laurent Tiers ◽  
Christophe Junot ◽  
François Becher ◽  
...  

AbstractClinical Proteomics biomarker discovery programs lead to the selection of putative new biomarkers of human pathologies. Following an initial discovery phase, validation of these candidates in larger populations is a major task that recently started relying upon the use of mass spectrometry approaches, especially in cases where classical immune-detection methods were lacking. Thanks to highly sensitive spectrometers, adapted measurement methods like selective reaction monitoring (SRM) and various pre-fractionation methods, the quantitative detection of protein/peptide biomarkers in low concentrations is now feasible from complex biological fluids. This possibility leads to the use of similar methodologies in clinical biology laboratories, within a new proteomic field that we shall name “Clinical Chemistry Proteomics” (CCP). Such evolution of Clinical Proteomics adds important constraints with regards to the in vitro diagnostic (IVD) application. As measured values of analytes will be used to diagnose, follow-up and adapt patient treatment on a routine basis; medical utility, robustness, reference materials and clinical feasibility are among the new issues of CCP to consider.


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