Azzah Hana Abu Yamin*, Shaamala Parliya, Nurul Aina Khalid, Anasufiza Habib
1. Biochemistry Unit, Specialised Diagnostics Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, 50588 Kuala Lumpur, Malaysia.
*Corresponding author: Azzah Hana Abu Yamin.
CITATION: Abu Yamin, A. H., Parliya, S., Khalid, N. A., & Habib, A. (2026). Addressing the limitations of ion-exchange chromatography for the detection of argininosuccinic aciduria: a technical note. International Medical Research Journal, 12(1), 31–41. https://doi.org/10.63719/imrj.2026.12.01.003
ABSTRACT
Argininosuccinic aciduria is a rare inherited metabolic disorder caused by a deficiency of argininosuccinate lyase in the urea cycle metabolism. Elevated concentrations of argininosuccinic acid (ASA) in plasma and/or urine are considered pathognomonic. Amino acid analysis using ion-exchange chromatography remains the preferred and most widely used diagnostic approach; however, co-elution of the ASA with adjacent amino acids is a known limitation that may compromise accurate detection and quantification. Here, we describe and illustrate a practical optimisation of liquid chromatography to improve the separation of ASA. Analyses were performed using Biochrom Ultra Physiological Fluid chemical kits on the Biochrom 30 Amino Acid analyser. The optimised method achieved complete resolution of the ASA peak, improving from initial full co-elution with leucine to 100% peak separation. This easily implementable optimisation effectively overcomes the limitation of ASA co-elution for the diagnosis of argininosuccinic aciduria.
KEYWORDS: argininosuccinic aciduria, argininosuccinic acid, ion-exchange chromatography, co-elution, amino acid analysis
