Publications

The material below is provided to support scientific exchange. Any content about investigational therapeutics or investigational uses of locally approved products does not establish the safety or efficacy of these therapeutics or uses, and there is no guarantee of local regulatory approval.

For questions beyond a product’s authorized indications or for information not available here, please contact Alnylam Medical Information.

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

Publication Details

Bioanalysis

May 2023

Access Here

Author(s)

Valerie A Clausen¹, Karen H Cao¹, John M Gansner¹, Gabriel J Robbie¹, Jing-Tao Wu¹

Affiliations

¹Alnylam Pharmaceuticals, Cambridge, MA 02142, USA

Abstract

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.

Conclusions:

This assay has advantages over previously published POx quantitation methods, was validated in accordance with regulatory guidelines and accurately determined POx levels in humans.