A Sensitive Plasma THC Assay Still Needed Additional Forensic Validation
A low detection limit does not establish that an assay has answered every forensic identification question. A 2017 plasma cannabinoid method illustrates this clearly: the authors reported strong quantitative performance while expressly identifying validation steps needed for a different use.
What the method was designed to do
Andrenyak and colleagues developed gas chromatography–tandem mass spectrometry for THC, 11-hydroxy-THC, THCCOOH and CBD in human plasma. Their intended application was controlled research in which the administered cannabinoids were known.
The lower limits of quantification were 0.1 ng/mL for THC and 11-hydroxy-THC, 0.25 ng/mL for CBD, and 0.5 ng/mL for THCCOOH. These are analytical performance values in plasma. They are not whole-blood thresholds and do not define impairment.
Quantification and identification need different checks
The investigators evaluated blank plasma from six sources and reported accuracy, precision and recovery experiments. They also collected a second set of mass-spectrometric transitions that could support ion-ratio monitoring.
However, recording another transition is not the same as validating an identification rule based on the ratio between transitions. The paper explained that its procedures met many, but not all, forensic validation requirements. Ion-ratio validation and a fuller assessment of interference from other drugs remained relevant before extending the assay to forensic unknowns.
How to use the limitation fairly
The correct reading is not that the published concentrations are automatically unreliable. The method was developed for a stated research purpose and demonstrated performance relevant to that purpose. The limitation concerns transferring that evidence to cases with uncertain exposure histories and potentially interfering substances.
A case review should therefore examine the laboratory’s own current validation, its identification criteria, the specimen matrix and the actual chromatographic evidence. Later work by a laboratory may address issues that the original publication did not.
Even complete identification and accurate quantification leave a further question: what does the concentration establish about the person’s condition? Our explanation of THC blood levels and impairment separates the chemical measurement from that functional conclusion.
Primary research
David M. Andrenyak and colleagues. Journal of Analytical Toxicology (2017). Determination of ∆-9-Tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC and Cannabidiol in Human Plasma using Gas Chromatography–Tandem Mass Spectrometry.
