Simultaneous determination of guanidinoacetate, creatine and creatinine in urine and plasma by un-derivatized liquid chromatography-tandem mass spectrometry

This version was published on 1 November 2008

Ann Clin Biochem 2008;45:575-584
© 2008 Association for Clinical Biochemistry


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Original Articles

R S Carling1,
S L Hogg1,
T C Wood2 and
J Calvin1

1 Biochemical Genetics Unit, Box 247, Addenbrookes Hospital, Hills Road, Cambridge CB2 0QQ, UK;
2 Biochemical Genetics Laboratory, Greenwood Genetic Center, 125 Gregor Mendel Circle, Greenwood SC 29646, USA

Corresponding author: Dr R S Carling. Email: rachel.carling{at}

Background: Creatine plays an important role in the storage and transmissionof phosphate-bound energy. The cerebral creatine deficiencysyndromes (CCDS) comprise three inherited defects in creatinebiosynthesis and transport. They are characterized by mentalretardation, speech and language delay and epilepsy. All threedisorders cause low-creatine signal on brain magnetic resonancespectroscopy (MRS); however, MRS may not be readily availableand even when it is, biochemical tests are required to determinethe underlying disorder.

Methods: Analysis was performed by liquid chromatography-tandem massspectrometry in positive ionization mode. Samples were analysedunderivatized using a rapid ‘dilute and shoot’ approach.Chromatographic separation of the three compounds was achieved.Stable isotope internal standards were used for quantification.

Results: Creatine, creatinine and guanidinoacetate were measured with a 2.5 minute run time. For guanidinoacetate, the standard curve was linear to at least 5000 µmol/L and for creatine and creatinine it was linear to at least 25 mmol/L. The lower limit of quantitation was 0.4 µmol/L for creatine and guanidinoacetate and 0.8 µmol/L for creatinine. Recoveries ranged from86% to 106% for the three analytes. Intra- and inter-assay variationfor each analyte was <10% in both urine and plasma.

Conclusion: A tandem mass spectrometric method has been developed and validatedfor the underivatized determination of guanidinoacetate, creatineand creatinine in human urine and plasma. Minimal sample preparationcoupled with a rapid run time make the method applicable tothe routine screening of patients with suspected CCDS.

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