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HPLC-(Q)-TOF-MS-Based Study of Plasma Metabolic Profile Differences Associated with Age in Pediatric Population Using
Oihane E Albóniga1,2, Oskar González-Mendia3, María E Blanco1
1Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain.
Insights
Plasma metabolic profiling in piglets reveals significant age-related changes in lipid metabolism. This study highlights specific lipids like lysophosphatidylcholines, crucial for understanding pediatric drug development.
Area of Science:
- Biochemistry
- Pediatric Pharmacology
- Metabolomics
Background:
- Accurate drug dosing in pediatrics requires understanding biological development.
- Invasive tissue sampling for organ maturation studies is challenging.
- Plasma offers a non-invasive surrogate for assessing organ metabolism.
Purpose of the Study:
- To investigate age-related metabolic profiles in piglet plasma.
- To identify key metabolites reflecting developmental changes.
- To establish plasma metabolomics as a tool for pediatric research.
Main Methods:
- Plasma samples from piglets of different ages (newborn, infant, child) analyzed using HPLC-(Q)-TOF-MS.
- Multiblock principal component analysis (MB-PCA) and partial least squares-discriminant analysis (PLS-DA) applied for data analysis.
- Univariate analysis to identify significant discriminatory metabolites.
Main Results:
- MB-PCA improved clustering compared to classical PCA.
- PLS-DA effectively separated age groups, validated by bootstrapping and permutation testing.
- Significant age-discriminatory metabolites identified: 13 in positive and 21 in negative ionization modes.
- Key identified metabolites include acylcarnitine, glycerophospholipids, lysophosphatidylcholines, and lysophosphatidylethanolamines.
Conclusions:
- Plasma metabolomics can effectively track age-related biological development in piglets.
- Lipid metabolism, particularly involving lysophosphatidylcholines and lysophosphatidylethanolamines, undergoes significant changes with age.
- These findings support plasma as a valuable matrix for pediatric drug development and metabolic studies.
Abstract:
A deep knowledge about the biological development of children is essential for appropriate drug administration and dosage in pediatrics. In this sense, the best approximation to study organ maturation is the analysis of tissue samples, but it requires invasive methods. For this reason, surrogate matrices should be explored. Among them, plasma emerges as a potential alternative since it represents a snapshot of global organ metabolism. In this work, plasma metabolic profiles from piglets of different ages (newborns, infants, and children) obtained by HPLC-(Q)-TOF-MS at positive and negative ionization modes were studied. Improved clustering within groups was achieved using multiblock principal component analysis compared to classical principal component analysis. Furthermore, the separation observed among groups was better resolved by using partial least squares-discriminant analysis, which was validated by bootstrapping and permutation testing. Thanks to univariate analysis, 13 metabolites in positive and 21 in negative ionization modes were found to be significant to discriminate the three groups of piglets. From these features, an acylcarnitine and eight glycerophospholipids were annotated and identified as metabolites of interest. The findings indicate that there is a relevant change with age in lipid metabolism in which lysophosphatidylcholines and lysophoshatidylethanolamines play an important role.
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