Synchronous LC-MS/MS Detection of Medicaments Influencing ARR
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Solution Overview
Problem
Current methods for detecting primary aldosteronism, particularly through the plasma aldosterone concentration (PAC)/plasma renin activity (PRA) ratio (ARR), face challenges such as false positive or false negative results due to influences from various medications, requiring medication withdrawal, which poses risks to patients and complicates diagnosis.
Innovation Solution
A method using liquid chromatography-tandem mass spectrometry for synchronous screening of medications influencing ARR values, allowing for qualitative detection of renin activity without medication withdrawal, thereby reducing false positives and negatives and improving diagnostic accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If medication withdrawal is performed to avoid false positive or false negative results, then detection accuracy is improved, but patient safety deteriorates and diagnostic complexity increases
Solution Approach 1:
The patent introduces an intermediary substance (internal standard) that does not interfere with the detection of target medications. This internal standard allows the detection system to distinguish between the target medications and other substances in the patient sample, enabling accurate detection without requiring medication withdrawal. The intermediary substance acts as a reference that maintains detection accuracy while allowing medications to remain in the patient's system.
Solution Approach 2:
The patent replaces the mechanical approach of medication withdrawal (physically removing the interfering substance) with a chemical/detector-based approach. Instead of withdrawing medications to eliminate interference, the system uses advanced detection technology with specific reagents and internal standards to identify and measure medications while ignoring their interfering effects on ARR detection. This substitution eliminates the need for medication withdrawal while maintaining detection accuracy.
2Measurement precision
If medication withdrawal is performed to avoid false positive or false negative results, then detection accuracy is improved, but diagnostic time and complexity increase
Solution Approach 1:
The patent performs preliminary actions by pre-establishing a detection system that includes specific reagents, internal standards, and detection protocols designed to be resistant to medication interference. This preliminary preparation allows the detection to be performed immediately without requiring prior medication withdrawal, eliminating the time loss associated with withdrawal periods while maintaining high detection accuracy.
Solution Approach 2:
The patent replaces the time-consuming mechanical process of medication withdrawal with a rapid chemical detection process. The advanced detection system uses specific reagents and internal standards that enable immediate identification of medications and their effects on ARR, eliminating the need for waiting periods associated with medication withdrawal and significantly reducing diagnostic time.
3Ease of operation
If traditional immunoassay methods are used for ARR detection, then detection process is simple, but detection accuracy deteriorates due to cross-reaction and lack of specificity
Solution Approach 1:
The patent introduces an intermediary substance (internal standard) that serves as a reference for accurate measurement. This internal standard allows the detection system to distinguish between the target medications and other substances, providing high specificity and accuracy while maintaining operational simplicity. The intermediary substance enables precise measurement without requiring complex sample preparation or medication withdrawal protocols.
Solution Approach 2:
The patent changes the detection parameters by using advanced detection technology with specific reagents and internal standards that are resistant to interference from medications. This parameter change enables the system to maintain high accuracy and specificity while keeping the detection process simple. The modified detection parameters allow for accurate measurement even in the presence of interfering substances, eliminating the need for complex pre-treatment procedures.
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 enhances the accuracy of ARR detection by simultaneously screening for medications affecting the ratio, reducing the risk of medication withdrawal and improving clinical judgment and application, providing a more reliable method for diagnosing primary aldosteronism.
Implementation Method 1
liquid chromatography-tandem mass spectrometry
Implementation Method 2
liquid chromatography-tandem mass spectrometry
Implementation Method 3
adding a protein precipitant containing an internal standard
Data Source
AI summary
The present invention provides a synchronous detection method of medicaments influencing ARR in the detecting process of renin activity by liquid chromatography-tandem mass spectrometry. The method achieves the qualitative screening of medicaments influencing ARR values while detecting plasma renin activity by liquid chromatography-tandem mass spectrometry; moreover, the method can be used to assist to analyze and judge ARR as negative, positive, false negative or false positive. The detecting method achieves effective extraction of angiotensin I and 43 hypertension therapeutics synchronously through protein precipitation to samples, and enables to perform synchronous detection of a plurality of indices including angiotensin I and 43 hypertension therapeutics on the extracted sample by liquid chromatography-tandem mass spectrometry technology of high throughput, high specificity and high sensitivity. Moreover, the detection method utilizes the MRM mass spectrum parameters for preliminary screening of the medicaments, and rechecks the medicaments according to the retention time thereof. The ARR detection value is combined with the medicament screening result for co-analysis, which effectively distinguishes the false positive or false negative result of the detection while avoiding the patient's withdrawal of medicament for treatment, thereby improving the detection accuracy of the actual primary aldosteronism, and facilitating clinical promotion and application.