1. Prepared by: Haya AL Nufaie Supervised by: Dr- Taghreed & Dr- Hana pharmacognocy Department, College of Pharmacy, King Saud University, Kingdom of Saudi Arabia Methadone can be used to replace the opioid drug that a person is dependent on. It prevents withdrawal symptoms and cuts down on the person's drug cravings. Methadone is long-acting; users only need one dose every 24 hours. Other opioids, such as heroin, require much more frequent doses in order to avoid withdrawal. When it's diluted in juice and prepared as a drink, it doesn't have a euphoric effect or interfere with a person's thinking. However, it does block the euphoric effect of heroin and other opioid drugs. Methadone works best when it is combined with other services, such as drug counselling and case management.  Using methadone allows opioid dependent people to stabilize and improve their lives.  People who use opioid drugs and who are infected with HIV or hepatitis C can take methadone to help protect their health and to reduce the risk of the spread of infection through needle sharing. INTRODUCTION WHAT IS METHADONE? WHY DO PEOPLE NEED IT? SIDE EFFECT SYNTHESIS OF METHADONE  solid phase microextraction: For quantitative analysis. The proposed procedure allows the extraction of methadone from a urine matrix. avoiding sample handling and saving evaporation of solvents and concentration steps. A fiber coated with polymethylsiloxane was employed for the extraction of methadone from urine and subsequently directly injected into the GC/MS.  Methadone Test Device (Urine): A rapid, one step test for the qualitative detection of Methadone in human urine  High-performance liquid chromatographic analysis: The method employed organic solvent extraction, enantiomeric separation on a Chiral AGP column, and ultraviolet absorption detection at 212 nm.  A liquid chromatography–tandem mass spectrometry (LC–MS/MS): Method for the chiral analysis of methadone, EDDP and EMDP was developed using an α-glycoprotein (AGP) stationary phase. The method development involved the utilisation of factorial analysis experimental designs and the application of artificial neural networks (ANNs) to model the chromatographic response surfaces. The optimal conditions were determined to be 20 mM acetic acid: isopropanol (93:7, pH 7.4), with a flow rate of 0.9 mL/min. ANALYSIS gg  Methadone hydrochloride is a synthetic diphenylheptane- derivative opiate agonist. It is an analgesic with the general properties of morphine.  Methadone is a racemic mixture and levomethadone is the active isomer. Methadone is a narcotic pain reliever, similar to morphine. Methadone also reduces withdrawal symptoms in people addicted to heroin or other narcotic drugs without causing the "high" associated with the drug addiction Methadone is readily absorbed and is widely distributed in the tissues. It has a prolonged half life and is subject to accumulation Methadone is metabolised chiefly in the liver; the drug undergoes N-demethylation and cyclisation and does not appear to be conjugated. Metabolism of methadone to its two major metabolites, 2-ethylidene-1,5- dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1 -pyrroline (EMDP).  drowsiness,loss of appetite, stomach pain, dry mouth,  drowsiness, loss of appetite, stomach pain, dry mouth, sweatingdifficulty urinatingmood changesvision sweating, difficulty urinating, mood changes vision problems problems  Symptom of over dose small, pinpoint pupils small, pinpoint pupils, slow or shallow breathing, loss of consciousness, coma The reaction scheme for the synthesis of methadone begins with the alkylation the of anion of diphenylacetonitrile with 1-dimethyl amino-2-chloropropane which produces a mixture of two isomeric nitriles, one high-melting, (commonly referred to as methadone nitrile), 2,2-Diphenyl-4-di methylaminovaleronitrile and one low-melting (isomethadone nitrile, 2,2-Diphenyl- 3-methyl-4-dimethylamino- butyronitrile. The high-melting nitrile, upon reaction with ethyl magnesium bromide and subsequent hydrolysis gives methadone. prolonged use of methadone may lead to dependence of the morphine type. The withdrawal symptoms are similar to, but less intense and more prolonged, than those produced by morphine. They develop more slowly and do not usually appear until 24-48 hours after the last dose. DEPENDENCE HOW DOES IT WORK?