Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Primary Hyperoxaluria Screening and Monitoring: Quantitative Measurement of Plasma Oxalate by Gas Chromatography-Mass Spectrometry With High Sensitivity

  • Mehrdad Yazdanpanah (Department of Paediatric Laboratory Medicine, The Hospital for Sick Children) ;
  • Jessie Cameron (Department of Paediatric Laboratory Medicine, The Hospital for Sick Children) ;
  • Chandra Chappel (Department of Paediatric Laboratory Medicine, The Hospital for Sick Children) ;
  • Libin Yuan (Department of Paediatric Laboratory Medicine, The Hospital for Sick Children)
  • Received : 2023.04.27
  • Accepted : 2023.09.14
  • Published : 2024.05.01
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Abstract

Background: Plasma oxalate measurements can be used for the screening and therapeutic monitoring of primary hyperoxaluria. We developed a gas chromatography-mass spectrometry (GC-MS) assay for plasma oxalate measurements with high sensitivity and suitable testing volumes for pediatric populations. Methods: Plasma oxalate was extracted, derivatized, and analyzed by GC-MS. We measured the ion at m/z 261.10 to quantify oxalate and the 13C2-oxalate ion (m/z: 263.15) as the internal standard. Method validation included determination of the linear range, limit of blank, limit of detection, lower limit of quantification, precision, recovery, carryover, interference, and dilution effect. The cut-off value between primary and non-primary hyperoxaluria in a pediatric population was analyzed. Results: The detection limit was 0.78 µmol/L, and the linear range was up to 80.0 µmol/L. The between-day precision was 5.7% at 41.3 µmol/L and 13.1% at 1.6 µmol/L. The carryover was <0.2%. The recovery rate ranged from 90% to 110%. Interference analysis showed that Hb did not interfere with plasma oxalate quantification, whereas intralipids and bilirubin caused false elevation of oxalate concentrations. A cut-off of 13.9 µmol/L showed 63% specificity and 77% sensitivity, whereas a cut-off of 4.15 µmol/L showed 100% specificity and 20% sensitivity. The minimum required sample volume was 250 µL. The detected oxalate concentrations showed interference from instrument conditioning, sample preparation procedures, medications, and various clinical conditions. Conclusions: GC-MS is a sensitive assay for quantifying plasma oxalate and is suitable for pediatric patients. Plasma oxalate concentrations should be interpreted in a clinical context.

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References

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