Endogenous high‐performance liquid chromatography/tandem mass spectrometry interferences and the case of perfluorohexane sulfonate (PFHxS) in human serum; are we overestimating exposure?
Bibliographic record
Abstract
Perfluorinated acids have received increasing scientific attention due to their widespread global distribution, environmental persistence and bioaccumulation in wildlife and humans. For perfluorohexane sulfonate (PFHxS, C(6)F(13)SO(3) (-), m/z 399), all existing human data have been generated using high-performance liquid chromatography (HPLC) and its most sensitive tandem mass spectrometric (MS/MS) transitions (m/z 399/80 [SO(3)](-) or m/z 399/99 [SO(3)F](-)), but this may be problematic because of co-eluting endogenous steroid sulfates that share common fragmentation pathways. We examined the magnitude of over-reporting for PFHxS in pregnant women (n = 29), and in pooled serum of males, non-pregnant and pregnant females (n = 3, 100 samples per pool), by comparing m/z 399/80 and 399/99 data with an interference-free transition, m/z 399/119. PFHxS concentrations in pregnant women determined using m/z 399/80 and 399/99 (p < 0.05), but not m/z 399/119, were positively correlated to the response of the steroid sulfates. This led to an average overestimation of PFHxS by 1.5- and 4.7-fold, using m/z 399/80 and 399/99, respectively, and validated the use of m/z 399/119 for the first time. The interferences were a problem in all human serum samples, and analysis of pooled serum revealed statistically significant over-reporting by m/z 399/80 and 399/99 for pregnant women > non-pregnant women > men. The magnitude of over-reporting here represents a worst-case scenario, but the extent to which the published literature values are biased is unknown due to limited details of methods in existing reports. Instead of using the less sensitive m/z 399/119 transition, we showed that an alternative selection of column and mobile phase can allow for sufficient chromatographic separation of the interferences. In conclusion, it was shown that routine analytical methods are prone to systematically overestimating PFHxS concentrations in serum of men or women, but that this can be avoided by alternative chromatographic steps or MS/MS transitions.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.020 | 0.034 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".