Exploring how interlaboratory comparisons are improving the accuracy and standardization of phosphatidylethanol (PEth) testing for alcohol consumption measurement.
Imagine a biomarker so precise it could reveal a person's alcohol consumption patterns over several weeks with scientific objectivity. This biomarker exists—it's called phosphatidylethanol (PEth). As researchers and clinicians increasingly rely on PEth to make crucial decisions in healthcare, workplace safety, and legal settings, an urgent question emerges: how can we ensure that a PEth test performed in a laboratory in Switzerland yields the same result as one conducted in Sweden or the United States? This question sparked a fascinating scientific endeavor—an interlaboratory comparison that would put the world's PEth testing methods to the ultimate test.
The implications extend far beyond laboratory walls. When a patient being evaluated for a liver transplant claims abstinence, but their PEth test suggests otherwise, the consequences are profound 6 . Similarly, when researchers subclassify different types of steatotic liver disease, accurate measurement of alcohol consumption becomes critical for proper diagnosis and treatment 1 2 .
In a world where alcohol-related health conditions affect millions, the precision of our measuring tools matters more than ever. This is the story of how scientists across the globe are joining forces to standardize this powerful biomarker, ensuring that every drop of blood tells a consistent story.
Informing critical healthcare choices based on accurate alcohol consumption data
Providing objective evidence in workplace testing and legal proceedings
Ensuring consistent results across laboratories worldwide
To understand the scientific quest for measurement consistency, we must first grasp what makes PEth such a valuable marker. Phosphatidylethanol is not just another alcohol biomarker; it's a direct metabolite formed exclusively in the presence of ethanol. When alcohol enters the bloodstream, it triggers a unique reaction in cell membranes, transforming a common phospholipid into this distinctive compound that can be detected for 2-4 weeks after consumption 4 .
Traditional breathalyzer tests effective
Ethyl glucuronide (EtG) detection window
PEth provides long-term consumption insight
Monitoring alcohol use in patients awaiting liver transplantation 6
Identifying hazardous alcohol use that patients might not openly report 5
Ensuring safety in sensitive occupations 8
The most commonly measured form—PEth 16:0/18:1—has become the gold standard, but its accurate measurement presents unique challenges that demand scientific collaboration.
As PEth testing gained prominence, concerns emerged about potential variability between laboratories. Different equipment, methodologies, and sampling devices could theoretically yield different results from the same blood sample. To address this, researchers designed a comprehensive interlaboratory comparison, the results of which were published in 2025 3 .
The study followed a meticulous protocol to ensure fair and meaningful comparisons:
The coordinating laboratory at the University of Bern collected four authentic blood samples with varying PEth concentrations covering the clinically relevant range 3 .
These samples were applied to different dried blood spot sampling devices and shipped to participating laboratories worldwide 3 .
Each laboratory processed and analyzed the samples using their established methods and equipment.
Results were returned to the coordinating center for statistical analysis comparing each laboratory's reported values against the target concentrations.
The PEth concentrations in the test samples were strategically chosen to include levels close to important decision limits (20 ng/mL and 200 ng/mL) that often guide clinical interpretations about abstinence or heavy drinking 3 . This design specifically tested laboratories' abilities to accurately measure the most clinically consequential ranges.
When the results from multiple laboratories were compiled and analyzed, they revealed both impressive consistency and important variability in PEth measurement. The comprehensive assessment showed that 73% of participating laboratories successfully quantified all samples within acceptable limits 3 . Even more encouraging, over 90% of laboratories accurately measured at least one sample within these predefined limits.
| Performance Category | Percentage of Laboratories | Interpretation |
|---|---|---|
| All samples within acceptable limits | 73% | Excellent consistency |
| At least one sample within acceptable limits | >90% | Majority show basic competency |
| Variation outside acceptable limits | 27% | Highlights need for standardization |
Perhaps most importantly, the study identified specific factors contributing to measurement variability. The type of dried blood spot sampling device used emerged as a significant variable, suggesting that not all collection systems perform equally 3 . This finding has practical implications for clinics and researchers selecting blood collection methods.
| PEth Concentration Level | Clinical Significance | Laboratory Performance |
|---|---|---|
| Near 20 ng/mL | Cutoff for detecting alcohol consumption vs. abstinence | Moderate variability observed |
| Near 200 ng/mL | Threshold indicative of heavy alcohol consumption | Better consistency among laboratories |
| Higher concentrations (>300 ng/mL) | Marked alcohol use | Highest measurement consistency |
These findings are particularly relevant given recent research demonstrating that approximately 16% of patients with steatotic liver disease underreport their alcohol consumption 1 , and in some populations, the figure may be as high as 39.5% 2 .
When clinical decisions depend on accurate measurement, this variability takes on profound significance.
What does it take to measure PEth accurately? The process requires sophisticated equipment and carefully developed materials. The table below highlights key components used in PEth research and clinical analysis:
| Tool/Reagent | Primary Function | Importance in PEth Analysis |
|---|---|---|
| Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) | Separation and detection of PEth molecules | Gold standard method for precise PEth quantification 6 |
| Dried Blood Spot (DBS) Sampling Devices | Collection and stabilization of blood samples | Enables convenient transport and storage; different devices can affect results 3 |
| PEth Reference Materials | Calibration and quality control | Essential for ensuring measurement accuracy across laboratories and methods |
| Specialized Blood Collection Tubes | Preservation of blood samples | Maintains sample integrity from collection to analysis |
| Solvent Systems | Extraction of PEth from blood samples | Critical step that influences recovery and measurement accuracy |
This toolkit continues to evolve, with recent research exploring innovative approaches such as miniature mass spectrometers for potential point-of-care testing and investigating new PEth subspecies like Lyso-phosphatidylethanol that might offer additional insights 7 .
Sophisticated instruments like LC-MS/MS enable precise PEth quantification
Reference standards and reagents ensure measurement accuracy
Proper collection devices maintain sample integrity throughout the process
The interlaboratory comparison of PEth measurement represents more than just a quality control exercise—it embodies the scientific commitment to precision and reliability in service of better health outcomes. While the results demonstrate generally good consistency across laboratories, the identified variability underscores the need for continued harmonization of methods and standards.
Organizations like PEth-NET (The Society of PEth Research) have taken up this challenge, establishing ongoing interlaboratory comparison programs and working toward consensus guidelines 7 8 .
As one researcher noted, the goal is to ensure that "PEth values are comparable independent of the laboratory or sampling device used" 3 .
For patients and clinicians, this technical work translates to greater confidence in the test results that inform significant healthcare decisions.
For researchers, it means more reliable data for understanding the relationship between alcohol consumption and health conditions.
As PEth testing continues to reveal the hidden truth about alcohol consumption—from detecting underreported use in patients with liver disease to guiding treatment decisions in primary care 5 —the work to refine its measurement ensures that this powerful invisible yardstick remains both sharp and reliable. In the delicate balance between personal privacy and clinical necessity, between patient testimony and objective evidence, such precision matters more than we might imagine.