Subject(s)
Alcohol Drinking/adverse effects , Counterfeit Drugs/poisoning , Counterfeit Drugs/toxicity , Ethanol/adverse effects , Ethanol/economics , Adolescent , Adult , Aged , Child , Female , Humans , Iran , Male , Middle Aged , Young AdultABSTRACT
Recently, illegal sildenafil analogues have emerged, causing serious social issues. In spite of the importance of sildenafil analogues, their metabolic profiles or clinical effects have not been reported yet. In this study, new metabolites of illegal sildenafil analogues such as hongdenafil, homosildenafil, and hydroxyhomosildenafil were determined using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS) and tandem mass spectrometry (LC-Q-TOF-MS/MS). To prepare metabolic samples, in vitro and in vivo studies were performed. For in vivo metabolites analysis, urine and feces samples of rats treated with sildenafil analogues were analyzed. For in vitro metabolites analysis, human liver microsomes incubated with sildenafil analogues were extracted and analyzed. All metabolites were characterized by LC-Q-TOF-MS and LC-Q-TOF-MS/MS. As a result, five, six, and seven metabolites were determined in hongdenafil, homosildenafil, and hydroxyhomosildenafil treated samples, respectively. These results could be applied to forensic science and other analytical fields. Moreover, these newly identified metabolites could be used as fundamental data to determine the side effect and toxicity of illegal sildenafil analogues.
Subject(s)
Counterfeit Drugs/analysis , Forensic Toxicology/methods , Phosphodiesterase 5 Inhibitors/analysis , Sildenafil Citrate/analysis , Urological Agents/analysis , Animals , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid/methods , Counterfeit Drugs/chemistry , Counterfeit Drugs/metabolism , Counterfeit Drugs/toxicity , Humans , Male , Microsomes, Liver/metabolism , Phosphodiesterase 5 Inhibitors/chemistry , Phosphodiesterase 5 Inhibitors/metabolism , Phosphodiesterase 5 Inhibitors/toxicity , Rats , Rats, Sprague-Dawley , Reference Standards , Sildenafil Citrate/analogs & derivatives , Sildenafil Citrate/metabolism , Sildenafil Citrate/toxicity , Tandem Mass Spectrometry/methods , Urological Agents/chemistry , Urological Agents/metabolism , Urological Agents/toxicityABSTRACT
A través de Internet recientemente se han comercializado algunas sustancias estimulantes estructuralmente parecidas a neurotransmisores derivadas de medicamentos ya retirados, que potencialmente pueden causar cuadros clínicos de diversa gravedad. Su efecto estimulante y el hecho de que aparecen antes de prohibirse su consumo explican la denominación genérica de legal highs. La exposición a estas sustancias se manifiesta como cuadros parecidos a los del consumo de productos como fenciclidina, anfetaminas o cocaína, ya que muy probablemente compartan mecanismos de acción sobre la recaptación de dopamina en los núcleos cerebrales implicados en el comportamiento de gratificación. La escasez de información médica contrastada, y las dificultades para disponer de material de calibración constituyen un reto diagnóstico. El desoxipipradol, sintetizado hace más de 6 décadas para el tratamiento del trastorno hipercinético, fue relegado por el metilfenidato, un compuesto análogo. En 2009 reapareció como droga recreativa responsable de algunos cuadros clínicos de intoxicación (AU)
Stimulant substances previously used for therapeutic purposes, and are currently banned, have recently been marketed through the Internet. These drugs, structurally similar to neurotransmitters, can potentially cause severe clinical conditions. Exposure to these 'legal highs' results in symptoms similar to those of well-known substances such as phencyclidine, amphetamines or cocaine, probably because they share mechanisms of action related to dopamine reuptake in brain nuclei involved in the regulation of reward behavior. The limitations of medical evidence, as well as difficulties in obtaining calibration material, constitute an analytical challenge. Desoxypipradol was synthesized more than six decades ago for the treatment of hyperkinetic disorder, but was surpassed by methylphenidate, a similar compound with a better pharmacokinetic performance. In 2009 desoxypipradol appeared as a recreational drug involved in several cases of clinical intoxication (AU)
