Yes. In Elliott’s 2004 investigation, changing the internal standard used in GC–MS analysis substantially changed some reported postmortem GHB concentrations. This was an analytical comparison on the specimens, not evidence that GHB had changed in the body between measurements. An exposure threshold cannot be interpreted responsibly without knowing how the laboratory measured GHB.
What did the method comparison actually include?
The preliminary comparison included nine blood and ten urine specimens from cases 1–5, including preserved and unpreserved variants. Those 19 specimens were not 19 independent people. Samples were examined using diethylene glycol (DEG) or deuterated GHB (GHB-d6) as internal standards in a derivatization GC–MS procedure. A separate GC–FID procedure was also compared.
An internal standard helps relate the analyte signal to a reference signal through preparation and measurement. It is not simply a label attached after analysis. A compound that behaves differently from the analyte, or encounters an interference, can affect the calculated concentration.
In Table II, urine specimen 5 gave GHB results of 80 and 82 mg/L with DEG, compared with 5 mg/L using GHB-d6. The GC–FID result was 9 mg/L. Such a difference could materially alter an interpretation based on a numerical threshold.
However, DEG did not always produce a higher result: blood specimen 7 gave 5 and 6 mg/L with DEG and 20 mg/L with GHB-d6. The findings do not support a universal multiplier for correcting every DEG-based measurement.
Why did the results differ?
The paper considered possible interference involving derivatized urea near the DEG retention time, as well as differences in extraction behavior. These were possible explanations, not proof that urea caused each discrepancy. The comparison supports investigating matrix-specific performance rather than assuming all historical results from one procedure share the same error.
The GC–MS method measured derivatized GHB without first converting it to gamma-butyrolactone (GBL). The GC–FID procedure converted GHB to GBL and measured total GBL, potentially including GBL already present. Its result therefore did not necessarily represent exactly the same chemical quantity. Agreement or disagreement between these methods needs that distinction.
The reported detection limits were 1 mg/L for GC–MS and 2.5 mg/L for GC–FID. A detection limit is not an exposure threshold, and the paper did not establish that a detected low concentration proves ingestion. Routine control material also did not reproduce every discrepancy seen in authentic postmortem specimens.
What did the accompanying 40-fatality series show?
Elliott also reported a three-month series of 40 fatalities in which GHB was not implicated in the cause of death. Blood was usually femoral, with carotid or iliac specimens in some cases. Samples were stored at 4°C and analyzed within ten days of receipt. The paper’s postmortem interval ran from certification of death to analysis, rather than simply from death to autopsy.
Using the GHB-d6 GC–MS method, unpreserved blood averaged 12.3 mg/L, range 2–29, in 38 specimens; fluoride-preserved blood averaged 12.6 mg/L, range 4–25, in 17. Unpreserved urine averaged 5.5 mg/L, range 0–18, in 39 specimens; preserved urine averaged 4.8 mg/L, range 0–10, in 15. These specimen counts overlap within the 40 cases and are not separate cohorts.
The proposed interpretive values of 30 mg/L in blood and 20 mg/L in urine were tied to this specific method and case material. The paper did not establish that concentrations above those values automatically prove intake.
What to request when reviewing a result
The useful records include the internal standard, chemical conversion steps, calibration, matrix validation, chromatograms and treatment of interference. Numerical quantitation does not itself establish antemortem exposure, impairment or cause of death. The separate problem of an unusable quantitative result is discussed in unquantifiable postmortem THC results.
Primary source
Elliott S. Further Evidence for the Presence of GHB in Postmortem Biological Fluid: Implications for the Interpretation of Findings. Journal of Analytical Toxicology. 2004;28(1):20–26. doi:10.1093/jat/28.1.20.
Leave a Reply