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Quantification of oxalate by novel LC–MS/MS: assay development, validation and application in lumasiran clinical trials: supplementary data

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posted on 2023-05-17, 12:26 authored by Valerie A Clausen, Karen H Cao, John M Gansner, Gabriel J Robbie, Jing-Tao Wu

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 K2EDTA) were

spiked with internal standard (13C2-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.


This study was funded by Alnylam Pharmaceuticals. VA Clausen, JM Gansner, GJ Robbie and J Wu are employees of Alnylam Pharmaceuticals and are shareholders or hold stock options from Alnylam Pharmaceuticals. KH Cao is a former employee of Alnylam Pharmaceuticals and is a shareholder of Alnylam Pharmaceuticals Medical writing and editorial assistance were provided by Peloton Advantage, LLC, an OPEN Health company, in accordance with Good Publication Practice (GPP3) guidelines, and funded by Alnylam Pharmaceuticals.