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Comprehensive Determination of Amino Acids for Diagnosis of Inborn Errors of Metabolism

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Analysis of clinically relevant amino acids using ion-exchange chromatography coupled to photometric detection has been an indispensable component in the detection of inborn errors of metabolism for six decades. Detection of amino acids using mass spectrometry offers advantages in speed and analytic specificity. Employing methanol extraction and controlled butylation, C8 reversed-phase chromatography, and MS/MS detection, 32 amino acids are quantified in 20 min with clinically appropriate imprecision in plasma, urine, and CSF. Quantitation is linear to 1,000 �mol/L and limits of detection are at least 1.0 �mol/L. Important isobaric amino acids are distinguished by chromatography or by unique patterns of fragmentation following collision-induced dissociation. The technique employs commercially available reagents and may be expanded and customized for specific clinical or research settings.
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