Dried Blood Spot Monitoring of Teriflunomide Levels
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Solution Overview
Problem
There is a need for a reliable and non-invasive method to monitor pharmaceutical drug plasma concentrations, particularly for teriflunomide, in pregnant subjects to ensure safe and effective treatment while minimizing harm to both the mother and fetus, as existing methods are complex and require specialized equipment.
Innovation Solution
A method involving a drop of blood deposited onto pre-treated filter paper with a stable-labeled internal standard, which can be analyzed using high-performance liquid chromatography mass spectrometry (LC-MS/MS), allowing for precise and reproducible monitoring of teriflunomide levels without the need for validated methods, and is effective across varying hematocrit values.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If existing methods are used to monitor drug plasma concentrations, then measurement capability is provided, but the methods are complex and require specialized equipment
Solution Approach 1:
The monitoring method is segmented into simple steps: collecting blood on pre-treated filter paper, drying the sample, and analyzing with LC-MS/MS. The filter paper is pre-treated with internal standard in discrete spots, dividing the complex analysis into manageable segments that can be performed in routine laboratories
Solution Approach 2:
The filter paper is pre-treated with internal standard before blood collection. This preliminary action ensures that the internal standard is already in place to capture and quantify the drug, eliminating the need for complex sample preparation steps during analysis
2Measurement precision
If invasive blood drawing methods are used, then accurate drug level monitoring is achieved, but patient comfort and safety are reduced
Solution Approach 1:
The method uses disposable filter paper cards that are pre-treated with internal standard. These single-use cards eliminate the need for repeated processing of expensive or sensitive equipment, allowing frequent monitoring with minimal invasiveness
Solution Approach 2:
The filter paper acts as an intermediary between the blood sample and the analysis equipment. It captures the drug and internal standard, allowing analysis without direct handling of liquid blood samples, thereby reducing invasiveness while maintaining accuracy
3Reliability
If validated methods are required for analysis, then measurement reliability is ensured, but the need for specialized facilities increases
Solution Approach 1:
The method is designed to be universally applicable in any facility equipped with LC-MS/MS, which is common in routine pharmacokinetic laboratories. The pre-treated filter paper and standardized protocol allow the same reliable measurement across different locations without requiring specialized validation at each site
4Measurement precision
If complex sample preparation is used, then analysis accuracy is improved, but processing time increases
Solution Approach 1:
The internal standard is pre-applied to the filter paper in controlled spots before blood collection. This eliminates the need for time-consuming internal standard addition and extraction steps during sample processing, reducing turnaround time while maintaining accuracy
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 quick, reliable, and non-invasive monitoring of teriflunomide plasma concentrations, ensuring safe drug levels and minimizing harm to the fetus, with results that can be obtained in any facility equipped with LC-MS/MS, facilitating effective treatment management.
Implementation Method 1
extracting a drug from a dried blood spot (DBS) sample
Implementation Method 2
performing mass spectrometry on the extracted DBS sample
Data Source
AI summary
Provided herein are methods for monitoring treatment for multiple sclerosis in a pregnant subject, and determining the efficacy of a treatment for multiple sclerosis in a pregnant subject. These methods include (a) extracting a drug from a dried blood spot (DBS) sample from a pregnant subject after a treatment for multiple sclerosis has been administered to the pregnant subject; (b) performing mass spectrometry on the extracted DBS sample; (c) determining a peak area ratio of the extracted DBS sample to an internal standard; and (d) identifying the administered treatment as being below the internal standard threshold if the plasma concentration of the treatment is less than 1 as compared to the internal standard ratio. 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.