Six HHC Cases Showed Different Concentrations in Blood and Plasma
HHC concentrations differed substantially between whole blood and plasma in a small casework series. The observed blood-to-plasma ratio came from six HHC-positive cases; it should not be turned into a universal conversion factor or an impairment threshold.
An analytical method with a small HHC application
The researchers validated an LC–MS/MS assay measuring THC, two THC metabolites, CBD and HHC. It was applied in routine forensic casework, including six cases in which both blood and plasma were available for HHC analysis.
HHC plasma concentrations ranged from 2.1 to 37.0 micrograms per liter, while blood concentrations ranged from 0.6 to 9.1 micrograms per liter. The reported blood-to-plasma ratio was approximately 0.28, with individual ratios from 0.24 to 0.39.
Two kinds of matrix comparison must be separated
The laboratory demonstrated that plasma-based calibration could quantify analytes added to whole blood within its validation criteria. That is an analytical calibration finding.
It does not mean that authentic whole blood and separated plasma contain identical concentrations after exposure. In the HHC cases, the paired specimens showed that these physiological matrices could yield different numerical values even when analyzed with the same validated workflow.
The HHC result combined two forms
The method did not chromatographically separate the 9R and 9S HHC diastereomers; it reported their combined HHC concentration. It also did not measure HHC metabolites.
An isotope-labeled HHC internal standard was unavailable during development, so the assay used labeled THC for HHC quantitation. The authors identified a matched HHC internal standard and expanded metabolite coverage as improvements. These limitations should accompany comparisons with methods that measure different HHC targets.
What six observations cannot resolve
Consumption histories and the timing between the vehicle-related event and blood collection were not available. The HHC case series did not establish a concentration–performance relationship or a validated model for back-calculating event-time concentrations.
The paper’s main experimental contribution is analytical measurement. Its general discussion of impairment does not substitute for a controlled HHC driving study. A case review should retain the actual specimen matrix and assay definition before considering any broader interpretation.
Related: Interpreting THC concentration and impairment.
Primary research
Quantification of ∆9-tetrahydrocannabinol, 11-OH-THC, THC-COOH, hexahydrocannabinol, and cannabidiol in human plasma and blood by liquid chromatography–tandem mass spectrometry. DOI: 10.1093/jat/bkae094.
