Quantification of oxalate by novel LC-MS/MS: assay development, validation and application in lumasiran clinical trials.

Background: Measurement of plasma oxalate (POx) is challenging, but critical, for management of patients with primary hyperoxaluria type 1. A novel LC-MS/MS assay was developed, validated and used to quantify POx in patients with primary hyperoxaluria type 1. Methods: Samples (100 μl of plasma in K 2 EDTA) were spiked with internal standard ( 13 C 2 -labeled oxalic acid), acidified and cleaned by protein precipitation before analysis using anion HPLC-ESI-MS/MS. The assay was validated with a quantitation range of 0.500-50.0 μg/ml (5.55-555 μmol/l). All parameters successfully met acceptance criteria, including 15% (20% at lower limit of quantification) for accuracy and precision. Conclusion: This assay has advantages over previously published POx quantitation methods, was validated in accordance with regulatory guidelines and accurately determined POx levels in humans.