Key result
LC-MS/MS assay boosts plasma renin activity sensitivity 140-fold vs enzyme immunoassay to measure near-complete inhibition.
Why the study?
Plasma renin activity is an important biomarker for renin inhibitors, but existing assays lacked sufficient sensitivity for precise measurement.
A novel LC-MS/MS assay for plasma renin activity provides 140-fold greater sensitivity than traditional enzyme immunoassays, facilitating better target engagement assessment for renin inhibitors.
May refine PRA measurement for renin inhibitor trials; leaves open clinical adoption pending broader validation.
BACKGROUND: Renin catalyzes the conversion of angiotensinogen to angiotensin I (Ang I), the first and rate-limiting step in the renin-angiotensin-aldosterone system. Plasma renin activity (PRA) is an important target engagement biomarker in the clinical development of renin inhibitors. We have developed and validated an improved PRA assay that incorporates an Ang I trapping antibody followed by extraction and quantification of Ang I using a highly sensitive and specific LC-MS/MS method. RESULTS: The following assay performance characteristics were assessed as part of analytical validation: precision, LOQ, spike recovery, dilution linearity, stability, absolute recovery and biological variability. The assay demonstrated excellent performance characteristics. Notably, the sensitivity of the assay was increased 140-fold when compared with a previous enzyme immunoassay-based assay. CONCLUSION: The improved sensitivity allowed the measurement of >95% PRA inhibition from baseline levels. In addition, we compared the LC-MS/MS-based assay to an enzyme immunoassay-based assay.
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Chappell et al. (2012) studied this question. LC-MS/MS method for plasma renin activity measurement vs. Enzyme immunoassay-based assay was evaluated on Assay sensitivity and performance characteristics (140-fold increase in sensitivity). An improved LC-MS/MS-based assay for plasma renin activity demonstrated a 140-fold increase in sensitivity compared to a previous enzyme immunoassay, allowing measurement of >95% PRA inhibition.
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