Desenvolvimento de metodologias analíticas para a determinação de metadona, buprenorfina e seus principais metabolitos em amostras biológicas : aplicações em contexto forense

Abstract

Throughout human history, almost all countries and cultures contacted situations of use and abuse. Since the drugs have always been used for several reasons among which may highlight religious reasons, medical reasons and reasons related to recreation and fun. Today the question of drug associates a wide variety of social and economic problems of which we highlight the crime, violence and neglect of family life. Thus, the process of treatment and rehabilitation related to this use and abuse of drugs is of great importance and must pass through several phases, including substitution treatment, keeping in view the future person's reintegration into society. It has been proven scientifically that substitution treatment can help reduce crime, infectious diseases and deaths related to drug use, as well as improved physical wellbeing, psychological and social development of drug addicts. Substitution treatment is by definition a form of medical treatment for opiate addicts (notably heroin) based on the use of a drug with similar action to the drug normally consumed. This treatment usually includes a maintenance period during which the patient is given a sufficient amount of substance in order to reduce risk behaviors and injuries related to consumption and another for detoxification, in which the amount of drug consumed will gradually reduced until it reaches the absence of consumption. Methadone and buprenorphine are two substances that can be used in substitution treatment in opioid-dependent people. The replacement substances may be agonists - substances that activate the opiate receptors in the brain, triggering the effect of drug use - or agonist-antagonists - which simultaneously activate the opiate receptors in the brain and limit or eliminate the effects other opiates or opioids consumed. There are other substances such as buprenorphine, which combine the characteristics of agonistic and antagonistic. The substitutes used heroin abuse are opiates - substances derived from opium poppy such as morphine or codeine, and heroin produced from morphine - or opioids - synthetic substances with effects similar to opiates such as buprenorphine or methadone. Methadone is a synthetic difenilpropilamina used in detoxification treatment and temporary maintenance of narcotic addiction and treatment of acute and chronic pain. Methadone has many of the pharmacological properties of morphine, and its analgesic potency similar. Unlike morphine, repeated administration of methadone causes marked sedative effects due to accumulation of this drug in the body. The syndrome of weaning from methadone is qualitatively similar to morphine, differing in fact be less intense and develop in a slower, gradual and prolonged. For these reasons, methadone is used in the management of narcotic addiction, perhaps eliminating the need for illicit opiate drugs. It is administered intramuscularly for analgesia and orally for maintenance therapy. After ingestion the drug is well absorbed from the gastrointestinal tract and widely distributed by the liver, lungs, kidneys, spleen, blood and urine. The reason of methadone bind to a large extent to tissue proteins may explain their cumulative effects. The metodona is rapidly metabolized after ingestion, in its primary metabolite, the normethadone. However, if rarely normethadone detect, as they dehydrate quickly giving rise to another compound, 2-ethylidene-1 ,5- dimethyl-3 ,3-difenilpirrolidina (EDDP). The EDDP is then demethylated to form 2- ethyl-5-methyl-3 ,3-diphenyl-1-pyrroline (EMDP), and the metabolite of methadone with more interest in being detected. Buprenorphine acts as a partial agonist at μ opioid receptors and as antagonist k. Its activity in the maintenance treatment of opioid dependence is attributed to its slow and reversible binding to receptors μ inducing a reduced need for drug addict by the patient over a period of time. Buprenorphine has a wide safety margin, due to its partial agonist activity of opioids, which limits its depressant effects, particularly at the level of heart and lung function. This substance is metabolized in the liver to Ndialquilbuprenorfina (norbuprenorphine) metabolites and glucuronide conjugate. The use of these drugs for substitution therapy in drug rehabilitation has been shown to be effective and safe, however there is the possibility of their misuse and consequently the occurrence of deaths associated with consumption of higher doses to treatment. Thus, the existence of specific and sensitive analytical methodologies for determining these substances in biological matrices, it is very important in forensic toxicology.