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Although 1-(2-phenethyl)-4-(N-propionylanilino)piperidine (fentanyl) is controlled by drug control laws, its slightly modified compounds, which show the same analgesic activities, cannot be controlled legally. Among these fentanyl analogues, 1-[2-(2-methylphenethyl)]-4-(N-propionylanilino)piperidine (α-methylfentanyl) is the typical and most widely abused drug and its overdose has caused a number of fatalities. Analysis of the urine of addicts has been widely performed to detect its metabolites and the unchanged compound for proof of its abuse. In this case, the metabolites detected in urine should reflect the structure of the original compound. In the present report, for clarification of α-methylfentanyl abuse, four novel metabolites, which reflect the original structure of α-methylfentanyl, were identified in rat urine. One of these was the p-hydroxy form of the aromatic ring of the α-methylfentanyl phenethyl group (mono-aromatic hydroxy α-methylfentanyl), while the second and third ones were metabolites of ω-1 or ω position hydroxypropionyl of α-methylfentanyl (mono-hydroxypropionyl α-methylfentanyl). The fourth one was a metabolite involving the p-hydroxy form of the aromatic ring of the phenethyl group and ω position of hydroxypropionyl α-methylfentanyl (di-hydroxy α-methylfentanyl). The structures of these compounds were identified by comparisons of their retention times and mass spectra obtained by gas chromatography-mass spectrometry (GC/MS) and mass chromatography of mono-and di-hydroxy α-methylfentanyl with those of the synthesized authentic compounds.

Arsine (AsH(3))-exposed human blood samples were analyzed by high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for arsenic speciation. After exposure of human blood samples to AsH(3) vapor for 90 min at room temperature, partial hemolysis was observed. Plasma samples from these whole blood samples were prepared by centrifugation at 1600 x g for 10 min and analyzed by HPLC-ICP-MS. In addition to arsenite [As(III); degraded from AsH(3)], an unidentified arsenic species (As-adduct) was detected at a retention time of 1.1 min. Following ultrafiltration of the plasma samples using a molecular weight cut-off of 10 kDa, As-adduct was not detected in the filtrate. To clarify the origin of As-adduct, AsH(3) was added to blank plasma and As(III) was added to both whole blood and hemolyzed blood. Although As(III) was detected in all samples, As-adduct was not detected. These results indicate that As-adduct was derived from erythrocytes during the process of hemolysis by AsH(3) and further suggest that As(III) and plasma ingredients do not contribute to As-adduct production. Therefore, the presence of As-adduct in blood could represent an indicator of acute arsine poisoning.

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