Beware of misattributing 'modafinil' in diphenhydramine-positive cases.

PURPOSE: Diphenhydramine is an antihistaminic agent available in numerous over-the-counter preparations, while modafinil is a wakefulness-promoting agent, available only by prescription, but also used recreationally, when purchased from the black market. Structurally, both substances belong to the class of so-called benzhydryl compounds, which can complicate their proper differentiation. The authors point out the possibility of misattributing modafinil in diphenhydramine-positive cases due to the likely coelution of nordiphenhydramine and modafinil.

METHODS

Post-mortem blood and vitreous humor samples were subjected to liquid-liquid extraction using ethyl acetate in an alkaline environment (pH = 9), followed by a detailed toxicological analysis utilizing ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry.

RESULTS

Through the application of full scan mode, multiple reaction monitoring (MRM), and product ion scan mode, the presence of modafinil was excluded in diphenhydramine-positive biological matrices (blood and vitreous humor).

CONCLUSIONS

In the analysis of benzhydryl compounds, particular caution should be exercised, with each case verified by comparison with a certified analytical standard, and, where possible, by detecting the metabolites of these compounds.