Abstract
Nonketotic hyperglycinemia (NKH), a metabolic disorder due to defects in the glycine cleavage system, leads to the accumulation of toxic levels of glycine. Glycine levels in these patients may be lowered by sodium benzoate treatment. Benzoic acid binds to glycine to form hippurate, which is subsequently eliminated through the kidneys. At high concentrations, hippuric acid can crystallize in the kidneys and cause renal failure. Therefore, it is desirable to have benzoic acids concentrations within a therapeutic range.
In the gas chromatography method described, the drug from the acidified serum or plasma sample is extracted using ethyl acetate. The organic phase containing drug is separated and dried under a stream of nitrogen. After trimethylsilyl derivatization, benzoic acid analysis is done on a gas chromatograph mass spectrometer. Quantitation of the drug in a sample is achieved by comparing responses of the unknown sample to the responses of the calibrators using selected ion monitoring. Benzoic acid D5 is used as an internal standard.
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References
Hoover-Fong, J.E., Shah, S., Van Hove, J.L., Applegarth, D., Toone, J. and Hamosh, A. (2004) Natural history of nonketotic hyperglycinemia in 65 patients. Neurology, 63, 1847–53.
Steiner, R.D., Sweetser, D.A., Rohrbaugh, J.R., Dowton, S.B., Toone, J.R. and Applegarth, D.A. (1996) Nonketotic hyperglycinemia: atypical clinical and biochemical manifestations. J Pediatr, 128, 243–6.
Applegarth, D.A. and Toone, J.R. (2001) Nonketotic hyperglycinemia (glycine encephalopathy): laboratory diagnosis. Mol Genet Metab, 74, 139–46.
Kure, S., Narisawa, K. and Tada, K. (1992) Enzymatic diagnosis of nonketotic hyperglycinemia with lymphoblasts. J Pediatr, 120, 95–8.
Hamosh, A., McDonald, J.W., Valle, D., Francomano, C.A., Niedermeyer, E. and Johnston, M.V. (1992) Dextromethorphan and high-dose benzoate therapy for nonketotic hyperglycinemia in an infant. J Pediatr, 121, 131–5.
Hamosh, A., Maher, J.F., Bellus, G.A., Rasmussen, S.A. and Johnston, M.V. (1998) Long-term use of high-dose benzoate and dextromethorphan for the treatment of nonketotic hyperglycinemia. J Pediatr, 132, 709–13.
Van Hove, J.L., Vande Kerckhove, K., Hennermann, J.B., Mahieu, V., Declercq, P., Mertens, S., De Becker, M., Kishnani, P.S. and Jaeken, J. (2005) Benzoate treatment and the glycine index in nonketotic hyperglycinaemia. J Inherit Metab Dis, 28, 651–63.
Sioufi, A. and Pommier, F. (1980) Gas chromatographic determination of low concentrations of benzoic acid in human plasma and urine. J Chromatogr, 181, 161–8.
Sarkissian, C.N., Scriver, C.R. and Mamer, O.A. (2007) Quantitation of phenylalanine and its trans-cinnamic, benzoic and hippuric acid metabolites in biological fluids in a single GC-MS analysis. J Mass Spectrom, 42, 811–7.
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Knoblauch, J.M., Scott, D.K., Smith, L.D., Garg, U. (2010). Determination of Benzoic Acid in Serum or Plasma by Gas Chromatography-Mass Spectrometry (GC/MS). In: Garg, U., Hammett-Stabler, C. (eds) Clinical Applications of Mass Spectrometry. Methods in Molecular Biology, vol 603. Humana Press. https://doi.org/10.1007/978-1-60761-459-3_11
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DOI: https://doi.org/10.1007/978-1-60761-459-3_11
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