Interest of nails analysis to investigate synthetic cannabinoid exposure? A case report

Abstract

Discuss the interest of nails analysis in the challenging investigation of synthetic cannabinoids (SC) exposure regarding the documentation of an acute intoxication by FUB-AMB (or AMB-FUBINACA or MMB-FUBINACA). A 20-year-old man was transferred to emergency department after report of a psychotic behavior since 6 days. His medical history and examination were unremarkable except for cannabis consummation and vaping habits. Toxicological investigations were performed in the seized e-liquid, in blood and urine sampled 12 h after hospitalization and in keratinous matrices sampled 23 days later: 4 cm length brown hair, fingernails and toenails clippings. After washing, (i) hair sample has been segmented, cut into small pieces and 20 mg were incubated 1 h at 60 °C in methanol, (ii) nails were mechanically grinded in fine powders and extraction was performed in methanol for 16 h at room temperature. Large toxicological screenings (CL-HRMS and CL-MS/MS) together with selective analysis were performed using previously published methods. FUB-AMB, detected in the e-liquid, was quantified in all biological samples: 227 and 55 ng/mL in serum and urine, respectively, and 570, 1250, 850 and 210 pg/mg in proximal hair segment (period of reported acute intoxication), distal hair segment, fingernails and toenails, respectively. Its major ester hydrolysis metabolite was detected in all biological samples except in hair. Ratio of signal of metabolite over parent substance is clearly higher in toenails than in fingernails: 57% versus 6%. To our knowledge, this case is the first report of FUB-AMB detection in nails. FUB-AMB main metabolite was detected only in nails, and was proportionally more important in toenails than in fingernails. Several elements can explain the differences in incorporation in keratinized matrices, e.g., absence of melanin in nail, way of incorporation depending on physicochemical properties of considered substance. In nails, foot sweating could have increased incorporation of metabolites and less frequent washing than hands reduce their elimination. In addition, FUB-AMB contain a labile ester. Strongly metabolized, this substance is weakly stable in blood in vitro at room temperature [Krotulski A et al. J Anal Tox 2021;45(1):60–85]. Whereas degradation of SC labile ester in hair was demonstrated [Franz F et al. Anal Bioanal Chem 2016;408(13):3445–52] their stability in nails is not demonstrated and, on the contrary, could be majored, especially in toenails. Nails analysis have to be interpreted cautiously. In this reported case, results in nails objectivized one or several former exposures to FUB-AMB without being able to specify their chronology nor their chronicity. While many studies investigate retrospective CS consumption using hair analysis, only one publication regarding SC in nails is reported in literature. This case illustrate the interest of this matrix to documented SC exposure but also, regarding all the parameters described, its potential use for prevalence studies of SC even if further investigations, such sensibility regarding more potent SC and occasional user, are required.