Plasma Renin Activity Measurement via LC-MS/MS
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Solution Overview
Problem
Current laboratory tests for measuring plasma renin activity are not cost-efficient and do not provide timely results, limiting frequent testing and diagnostic capabilities for disorders related to the renin-angiotensin-aldosterone system.
Innovation Solution
A method using mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine angiotensin I generation by plasma renin, incorporating a stable isotope-labeled internal standard and external calibration standards to quantify AngI levels accurately and efficiently.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of time
If traditional laboratory tests are used to measure plasma renin activity, then the testing process is simpler and less expensive, but the results are not timely and frequent testing is limited
Solution Approach 1:
The patent replaces traditional mechanical/chemical assay methods with mass spectrometry technology to measure angiotensin I levels. This substitution enables faster, more automated analysis with results obtainable within hours rather than days, directly addressing the time loss and testing frequency limitations of conventional methods
Solution Approach 2:
The invention changes the measurement parameter from indirect renin activity assessment to direct angiotensin I quantification using mass spectrometry. This parameter change enables more precise, rapid, and frequent monitoring of renin-angiotensin system activity, overcoming the temporal limitations of traditional tests
2Loss of energy
If traditional laboratory tests are used to measure plasma renin activity, then the testing procedure is less complex, but the results are not cost-efficient
Solution Approach 1:
The patent replaces complex, resource-intensive traditional assay procedures with mass spectrometry-based measurement. Although the instrument is sophisticated, the method eliminates multiple manual steps, reagents, and extended processing times associated with conventional tests, resulting in better cost-efficiency despite the advanced technology required
3Measurement precision
If mass spectrometry is used to measure AngI levels, then the measurement precision is improved, but the device complexity increases
Solution Approach 1:
The patent extracts and measures only the specific angiotensin I peptide of interest from the complex plasma matrix using mass spectrometry. By focusing the measurement on this single target molecule rather than assessing overall renin activity through indirect methods, the system achieves high measurement precision while managing device complexity through targeted analysis
Solution Approach 2:
The invention uses stable isotope-labeled angiotensin I as an internal standard to mediate the measurement process. This intermediary substance enables precise quantification by providing a reference point that compensates for variations in the mass spectrometry system, thereby maintaining high measurement precision despite the complexity of the instrumentation
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables sensitive and specific measurement of plasma renin activity, allowing for faster and more frequent testing, with an analytically measurable range of 0.167-66.667 ng/mL/hr, improving diagnostic capabilities for hypertension, aldosteronism, and adrenal insufficiency assessment.
Implementation Method 1
angiotensinogen, constitutively manufactured by the liver, is hydrolyzed by renin, an enzyme manufactured by the renal juxtaglomerular apparatus, to form AngI
Implementation Method 2
adding a protease; incubating the sample under conditions to allow the protease to hydrolyze the AngI to generate a defined AngI cleavage product
Implementation Method 3
ionizing the defined AngI cleavage product to produce one or more AngI cleavage product ions detectable by mass spectrometry
Data Source
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AI summary
Disclosed are methods and systems for the quantification of AngI and/or determination of plasma renin activity in a sample. The methods and systems disclosed herein can be useful for diagnosis of hypertension, aldosteronism and other abnormalities of the renin angiotensin aldosterone system (RAAS).