Where a THC Standard Is Added Matters in Dried Blood-Spot Validation

A cannabinoid standard added to an already dried blood spot may not behave like THC present in blood before the spot dries. A dried-spot study identified that preparation difference as a possible reason laboratories obtained very different extraction recoveries.

The validation question comes before the patient comparison

Researchers developed an LC–MS/MS method for THC and THC-COOH in approximately 20-microliter dried capillary blood spots. Their calibration and quality-control samples were made by adding standards to liquid blood before spotting and drying.

With the study’s two-step extraction, THC recovery exceeded 80% at the evaluated concentrations. Using other tested solvents alone produced much lower recovery. These are analytical extraction findings, not evidence that changing the method changes the amount originally circulating in a donor.

A convenient control may miss a difficult extraction step

In discussing disagreements with earlier methods, the authors distinguished fortifying blood before spotting from adding analyte to a spot afterward. The latter may not reproduce how the compound becomes retained within the dried specimen.

This was a proposed explanation for differences across studies, rather than a head-to-head proof that every earlier assay was invalid. Still, it identifies a concrete validation question: did the controls challenge the same drying and extraction processes as authentic specimens?

Good recovery did not resolve every collection problem

The clinical portion collected dried spots from 159 participants and venous samples from 90. Only subsets supplied quantitative paired comparisons. THC showed much greater capillary-to-venous variability than THC-COOH.

The authors considered fingertip contamination a possible explanation for extreme THC values. They did not experimentally establish that contamination caused every outlier. Successful extraction validation therefore did not eliminate uncertainty introduced before the sample reached the instrument.

How to assess a reported result

Review when standards and internal standards were introduced, how the specimen dried, and whether recovery was assessed in a preparation resembling the submitted sample. Also distinguish detection limits from quantification limits and values extrapolated above calibration.

This study concerns human blood specimens and laboratory performance. It did not establish a conversion from dried-spot THC to driving impairment, nor a universal correction applicable to every collection device or laboratory.

Related: Interpreting THC concentration and impairment.

Primary research

Determination of THC and THC-COOH in Dried Capillary Blood Spots and Comparison to Venous Blood of Recreational Cannabis Consumers in a Pilot Study. DOI: 10.1002/dta.70085.