Internal reference compounds labeled with stable isotopes have been used to quantify drugs and drug metabolites in urine, plasma and breast milk. [2,4,5J%&]Diphenylhydantoin, [2,4,5J3C3]phenobarbital and [I-CZH3]valium have been used to quantify diphenylhydantoin, phenobarbital and Valium, respectiv
High-precision mass spectrometric analysis using stable isotopes in studies of children
β Scribed by Henk Schierbeek; Chris H.P. van den Akker; Laurent B. Fay; Johannes B. van Goudoever
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 547 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0277-7037
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β¦ Synopsis
Abstract
The use of stable isotopes combined with mass spectrometry (MS) provides insight into metabolic processes within the body. Herein, an overview on the relevance of stable isotope methodology in pediatric research is presented. Applications for the use of stable isotopes with MS cover carbohydrate, fat, and amino acid metabolism as well as body composition, energy expenditure, and the synthesis of specific peptides and proteins, such as glutathione and albumin. The main focus of these studies is on the interactions between nutrients and the endogenous metabolism within the body and how these factors affect the health of a growing infant. Considering that the early imprinting of metabolic processes hugely impacts metabolism (and thus functional outcome) later in life, research in this area is important and is advancing rapidly. The major fluxes on a metabolic level are the synthesis and breakdown rates. They can be quantified using kinetic tracer analysis and mathematical modeling. Organic MS and isotope ratio mass spectrometry (IRMS) are the two most mature techniques for the isotopic analysis of compounds. Introduction of the samples is usually done by coupling gas chromatography (GC) to either IRMS or MS because it is the most robust technique for specific isotopic analysis of volatile compounds. In addition, liquid chromatography (LC) is now being used more often as a tool for sample introduction of both volatile and nonβvolatile compounds into IRMS or MS for ^13^C isotopic analyses at natural abundances and for ^13^Cβlabeled enriched compounds. The availability of samples is often limited in pediatric patients. Therefore, sample size restriction is important when developing new methods. Also, the availability of stable isotopeβlabeled substrates is necessary for measurements of the kinetics and concentrations in metabolic studies, which can be a limiting factor. During the last decade, the availability of these substrates has increased. Furthermore, improvements in the accuracy, precision, and sensitivity of existing techniques (such as GC/IRMS) and the development of new techniques (such as LC/IRMS) have opened up new avenues for tackling these limitations. Β© 2011 Wiley Periodicals, Inc. Mass Spec Rev 31:312β330, 2012
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