Stability of 11-Nor-Δ9-carboxy-tetrahydrocannabinol Glucuronide in Plasma and Urine Assessed by Liquid Chromatography-Tandem Mass Spectrometry

Background: Unconjugated 11-nor-Δ9-carboxy-tetrahydrocannabinol (THCCOOH) in blood and urine has been proposed as a valuable marker, but the glucuronide (THCCOOglu) is present in considerably higher concentrations than the parent drug. Acyl glucuronides have been shown to be potentially reactive conjugates, which may affect the in vitro metabolite pattern. Methods: Extraction procedures and a liquid chromatography-tandem mass spectrometry assay were developed and validated to investigate the stability of THCCOOglu in urine and plasma. Plasma and urine samples with added THCCOOglu were stored at −20, 4, 20, and 40 °C up to 10 days. Results: The glucuronide was stable at −20 °C in both matrices, whereas THCCOOglu concentrations decreased at all other storage conditions. For a given storage time and temperature, the decrease in plasma was higher than that in urine. At 20 °C, a marked change in concentration could be observed within 2 days of storage. Degradation of THCCOOglu followed an apparent first-order process and led to the formation of THCCOOH. The sum of the molar concentrations of both analytes corresponded only to the initial THCCOOglu in plasma and urine samples stored at 4 °C. Conclusions: The in vitro degradation of THCCOOglu prevents clinical conclusions based on the metabolite pattern or the concentration of unconjugated THCCOOH in samples stored at ≥4 °C for prolonged periods.