The synthetic cannabinoids 5F-QUPIC and MDMB-CHMICA were sprayed on plant material intended for smoking and was seized as a criminal evidence. Their presence was confirmed by gas chromatography – mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR). In the absence of analytical standards (indirect approach), the quantity of 5F-QUPIC in the herbal extract was determined by high-performance liquid chromatography with diode array detection (HPLC-DAD) based on total hydrolysis and measurement of the hydrolytic product (8-hydroxyquinoline) at 292 nm. The quantity of MDMB-CHMICA was determined using the ratio of 1H-NMR signals of both compounds in methanol-d4. 5F-QUPIC and MDMB-CHMICA in the herbal mixture were determined by the validated HPLC-DAD protocol by a direct approach with standards.

Background and Clinical Significance: Upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, is increasingly prescribed for autoimmune and inflammatory diseases. Although its therapeutic safety profile is well established, fatal intoxications have not been reported to date. Case Presentation: We describe the first fatal case of upadacitinib overdose in a 13-year-old girl. Following ingestion of approximately 600 mg (40 × 15 mg tablets Rinvoq^®), the patient presented with deep coma, profound bradycardia (~40 bpm) with third-degree atrioventricular block, conduction delay, hypotension, hypothermia, and metabolic acidosis. Laboratory tests showed hyperglycemia (17.8 mmol/L) and only minimal elevations in cardiac biomarkers (CK 57.03 U/L, CK-MB 30.64 U/L, troponin 0.003 ng/mL). Despite advanced resuscitation, the patient succumbed within a few hours. Forensic toxicology revealed extremely high concentrations of upadacitinib, 1.84 µg/mL (~1840 ng/mL) in blood and 70.3 µg/mL in gastric contents, far exceeding reported therapeutic plasma levels (Cmax 36.0 ± 8.8 ng/mL). This case establishes the first reported value for a lethal upadacitinib concentration in humans. The combination of conduction abnormalities, refractory shock, and minimal biomarker changes is consistent with an acute electrophysiological and hemodynamic collapse rather than myocardial infarction. Conclusions: The toxicity of upadacitinib in this case is characterized by profound central nervous system depression, severe cardiovascular (electrophysiological and hemodynamic) disturbances, and metabolic abnormalities (acidosis and hyperglycemia). These findings provide essential reference data for clinical and forensic toxicology, highlight the fatal potential of upadacitinib in overdose, and underscore the importance of secure medication storage and pharmacovigilance in households with adolescents.

Among the non-classical platinum complexes, Pt(IV) prodrugs are most promising as versatile scaffolds for structural modification and fine tuning of their activation-by-reduction mechanism of action and the resulting anticancer activity. Herein, four new asymmetrically disubstituted pyrenebutyrate complexes of Pt(IV) (2–5) were synthesized and thoroughly studied. In this series, the second axial ligand was derived from dicarboxylic acids of different length—4 and 5 C-atoms, or replacement of the C-atom in the middle with either O- or S-atom. The structural effects on reduction kinetics, lipophilicity and cellular internalization of the complexes were monitored by NMR, HPLC, fluorescence and ICP-MS measurements. Their cytotoxicity was tested on a panel of cancer cell lines and mechanistic insights were obtained from proteome analysis and microscope imaging. The data indicate that all complexes, especially complex 3, represent a promising class of Pt(IV) prodrugs, exhibiting significantly higher cytotoxic activity than cisplatin in all tested models, including a cisplatin-resistant line. This was explained with a stronger and more integrated apoptotic response than cisplatin: pronounced Bax upregulation (3.6-fold), maximal cleaved caspase-3 (4-fold), activation of both intrinsic and extrinsic pathways, and effective p53 Ser15/Ser46 phosphorylation. The consistent rank order of potency (3 > 4 > 5 ≈ 2 ≫ cisplatin) suggests that subtle ligand modifications can substantially enhance efficacy, possibly by improving cellular uptake or altering DNA binding.