In clinical toxicology (when prescribed in some special situations) as well as in forensic toxicology, hair general toxicological screenings (including more than 700 NPS) using LC-HRMS and LC-MS/MS are performed in our laboratory. We reported surprising positive hair results for 1-(2-methoxyphenyl)piperazine (2-MeOPP) in two cases of urapidil treatment, an in vitro metabolism study of urapidil investigated using human liver microsome (HLMs) and liquid chromatography with high-resolution mass spectrometry detection (LC–HRMS), and a retrospectively identification in blood and urine samples in one case.

(case #1) a 37-year-old man hospitalized for acute renal failure with bilateral kidney ischemia. Since he had admitted to regular cannabis use (a known promoting factor of renal ischemia), a hair analysis was prescribed in order to investigated for other addictions that might also be related to his illness (e.g. cocaine).

(case #2) a 55-year-old man who was found unconscious in the street after an altercation and died in hospital 2 months later. A forensic hair analysis was requested in order to investigate a putatively drug use at the time of the altercation (e.g. cocaine and heroin).

Non segmental hair (brown hair, 1.5cm-long, and brown hair, 4cm-long, in case #1 and #2, respectively) analysis were performed using both LC-HRMS and liquid chromatography with tandem mass spectrometry detection (LC-MS/MS) previously published methods [Gicquel T. Drug Test Anal 14(1):144–153; 2022]. In order to explain observed results, and owing to a hypothesis of 2-MeOPP presence related to urapidil metabolism urapidil [N. Allibe. Toxicol Anal Clin 26:128–132; 2014], incubation with HLMs was also performed [Gicquel T. Drug Test Anal 14(1):144–153; 2022].

In case#1, drugs related to patient's treatment since his hospitalization (3 weeks before), including urapidil (120mg/day), were detected in hair together with 2-MeOPP. Any possible intake of this NPS was denied by the patient.

In case #2, cocaine and related metabolites, medication related the treatment prescribed since the hospitalization (10 weeks before), including urapidil, were detected in hair together with 2-MeOPP.

Hair results were 650 and 0.6ng/mg (case#1), 410 and 4.4ng/mg (case #2) for urapidil and 2-MeOPP, respectively.

In vitro metabolism study confirmed that 2-MeOPP is a minor metabolite of urapidil (about 6%), and both were retrospectively detected in other case#1 biological samples: 140 and 11μg/L (blood), 3660 and 58μg/L (urine), for urapidil and 2-MeOPP, respectively.

These results exhibit (i) metabolism of urapidil to 2-MeOPP, and (ii) a significant incorporation of 2-MeOPP into hair as a minor metabolite of urapidil. The lack of analytical data in the literature about concentrations observed in 2-MeOPP users do not allow us to compare these results with cases of 2-MeOPP proven consumption. These cases highlight (i) the risk of detection of 2-MeOPP in biological samples (blood, urine and hair) in case of urapidil treatment, and (ii) the necessity to consider the metabolism of drugs commonly administered in hospital practice to avoid misinterpretation of hair analytical results.