Dried Blood Spot Teriflunomide Monitoring via LC-MS/MS
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Pregnant individuals face challenges in monitoring and maintaining appropriate drug plasma concentrations, particularly for teriflunomide, due to the complexity and invasiveness of existing methods, which can be harmful to both the mother and fetus if not managed correctly.
Innovation Solution
A method involving a drop of blood deposited onto pre-treated filter paper with a stable-labeled internal standard, allowing for accurate and non-invasive monitoring of teriflunomide levels using high-performance liquid chromatography mass spectrometry (LC-MS/MS), enabling quick, reliable, and reproducible plasma concentration analysis without the need for validated methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional plasma concentration monitoring methods are used, then accurate drug level measurement is achieved, but the process becomes complex and invasive, potentially harmful to pregnant subjects and fetuses
Solution Approach 1:
The patent extracts only the necessary component (dried blood spot) from the complex plasma separation process. Instead of requiring full plasma extraction and complex preparation, the method uses a simple dried blood spot on filter paper that can be directly analyzed, eliminating the need for complex centrifugation and plasma separation procedures while maintaining measurement accuracy
Solution Approach 2:
The filter paper is pre-treated with internal standard before blood collection. This preliminary action ensures that when blood is deposited on the paper, the internal standard is already in position to accurately quantify the drug concentration, eliminating the need for complex post-collection preparation steps and validation procedures
2Reliability
If traditional invasive monitoring methods are used, then drug concentration data is obtained, but the procedure becomes harmful to the pregnant subject and fetus
Solution Approach 1:
The patent uses a disposable dried blood spot on filter paper that requires minimal blood volume (a single drop). This disposable approach eliminates the need for repeated invasive procedures, reducing cumulative harm to the pregnant subject and fetus while providing reliable drug level data for treatment monitoring
Solution Approach 2:
The method changes the sample state from liquid plasma to dried blood spot, and changes the analysis approach from requiring large volumes to using trace analysis on the dried spot. This parameter change reduces the invasive nature of blood collection while maintaining the reliability of drug concentration measurements through stable isotope dilution mass spectrometry
3Measurement precision
If complex validated methods are used for drug analysis, then accurate results are obtained, but the process requires extensive validation and specialized facilities
Solution Approach 1:
The filter paper is pre-treated with a known amount of stable-labeled internal standard (ISTD) before blood collection. This preliminary action eliminates the need for complex validation procedures at each testing facility, as the internal standard is already in position to accurately quantify teriflunomide concentration through simple mass spectrometry analysis, making the method easily implementable in any facility with LC-MS/MS capability
Solution Approach 2:
The stable-labeled internal standard acts as an intermediary between the blood sample and the mass spectrometry analysis. It co-extracts with teriflunomide from the dried blood spot and provides a reliable reference signal, simplifying the analysis protocol and eliminating the need for complex validation while ensuring accurate concentration measurements
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 provides precise and reliable monitoring of teriflunomide levels in pregnant subjects, ensuring safe and effective treatment by determining if the drug concentration is within a non-toxic range for the fetus and the mother, facilitating adjustments to dosages as needed.
Implementation Method 1
performing mass spectrometry on the extracted DBS sample
Implementation Method 2
equipped with a high performance liquid chromatography mass spectrometer (LC-MS/MS)
Data Source
AI summary
Provided herein are systems that include: a mass spectrometry device configured to (i) generate a peak representing a drug in an extracted DBS sample from a pregnant subject after a treatment for multiple sclerosis to the pregnant subject has been administered and (ii) generate a peak representing an internal standard; a computer-readable memory including computer-executable instructions; and one or more processors communicatively coupled to the mass spectrometry device and configured to execute the computer-executable instructions, wherein when the one or more processors are executing the computer-executable instructions, the one or more processors are configured to carry out operations including: determining a peak area ratio of the drug in the extracted DBS sample to the internal standard; and identifying the administered treatment as being below an internal standard threshold when the peak area ratio of the drug in the extracted DB S sample to the internal standard is less than 1. Also provided herein are dried blood spot cards, and kits that include a dried blood spot card pre-treated with at least one internal standard.