An accurate stable isotope dilution gas chromatographic-mass spectrometric approach to the diagnosis of guanidinoacetate methyltransferase deficiency

E. A. Struys, E. E.W. Jansen, H. J. Ten Brink, N. M. Verhoeven, M. S. Van Der Knaap, C. Jakobs*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


A gas chromatography-mass spectrometry (GC-MS) method is described for the quantification of guanidinoacetate in different body fluids, using a two step derivatisation procedure which involves a reaction with hexafluoroacetylacetone to form a bis(trifluoromethyl)pyrimidine ring structure followed by a reaction with pentafluorobenzyl bromide. 13C2-labelled guanidinoacetate is used as an internal standard. Bis(trifluoromethyl)pyrimidine pentafluorobenzyl derivatives were separated on a polar capillary GC-column and were quantified using negative chemical ionisation mass fragmentography. The detection limit of the method is 1 pmol guanidinoacetate in a 100 μl sample. Control values were obtained for urine (53.9±25.9 mmol mol-1 creatinine), plasma (1.08±0.31 μmol l-1), cerebrospinal fluid (CSF) (0.114±0.068 μmol l-1) and amniotic fluid (3.44±0.64 μmol l-1). The applicability of the method is illustrated by the determination of guanidinoacetate in urine, plasma and CSF of a patient affected with guanidinoacetate methyltransferase deficiency. In all body fluids of this patient, guanidinoacetate was highly elevated. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)659-665
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Issue number4-5
Publication statusPublished - 1 Dec 1998

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