Subject(s)
Analgesics, Opioid/adverse effects , Counterfeit Drugs/adverse effects , Fentanyl/analogs & derivatives , Illicit Drugs/adverse effects , Opioid-Related Disorders/history , Analgesics, Opioid/chemical synthesis , Counterfeit Drugs/chemical synthesis , Fentanyl/adverse effects , Fentanyl/chemical synthesis , History, 20th Century , History, 21st Century , Humans , Illicit Drugs/chemical synthesis , Naloxone/administration & dosage , Narcotic Antagonists/administration & dosage , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/etiology , United States/epidemiologyABSTRACT
Multidimensional isotope profiling is a useful tool for the characterization of the provenance of active pharmaceutical ingredients (API). To evaluate this approach, samples of the nonsteroidal anti-inflammatory drug (NSAIDs) ibuprofen were collected from 32 manufactures and 13 countries, and carbon, hydrogen and oxygen isotope ratios were analyzed by elemental analyzer, chromium-filled elemental analyzer and high temperature conversion elemental analyzer (EA, Cr-EA and TC/EA) coupled to an isotope ratio mass spectrometry (IRMS). The range of isotope values of ibuprofen (δ(13)C: -33.2±0.1 to -27.4±0.1; δ(2)H: -121.4±1.5 to -41.2±0.8; and δ(18)O: -12.6±0.3 to 19.0±0.6) allowed characterization and distinction of 5 groups, which reflect synthetic pathways and/or use of different raw materials, as well as possible isotope fractionation during the synthesis reactions. This study highlights that multi isotope fingerprinting has potential for identification of sources, and provides a database of isotope composition of ibuprofen (δ(2)H, δ(13)C, δ(18)O) that might improve the tracing of origin, transport pathways and environmental fate of ibuprofen.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/analysis , Carbon Isotopes/analysis , Counterfeit Drugs/analysis , Hydrogen/analysis , Ibuprofen/analysis , Mass Spectrometry/methods , Oxygen Isotopes/analysis , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Counterfeit Drugs/chemical synthesis , Ibuprofen/chemical synthesis , Spectrophotometry, UltravioletABSTRACT
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)
