tailieunhanh - Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 21)

Introduction: There are a number of compounds, such as morphine and codeine, which are classified into the opium alkaloids (opiates). They are being used as ethical drugs of narcotic analgesics and antitussives; 1 % powder of codeine or dihydrocodeine is commonly included in over-the-counter drugs of antitussives. Figure shows metabolic pathways of morphine, heroin and codeine. Since morphine and codeine are finally excreted into urine in the conjugated forms with glucuronic acid [1–3], it is necessary to hydrolyze the conjugated forms of these compounds before GC/MS analysis. Heroin is rapidly deacetylated and finally excreted into urine as morphine. | Morphine and its analogues by Hideyuki Yamada and Kazuta Oguri Introduction There are a number of compounds such as morphine and codeine which are classified into the opium alkaloids opiates . They are being used as ethical drugs of narcotic analgesics and antitussives 1 powder of codeine or dihydrocodeine is commonly included in over-the-counter drugs of antitussives. Figure shows metabolic pathways of morphine heroin and codeine. Since morphine and codeine are finally excreted into urine in the conjugated forms with glucuronic acid 1-3 it is necessary to hydrolyze the conjugated forms of these compounds before GC MS analysis. Heroin is rapidly deacetylated and finally excreted into urine as morphine glucuronides. Therefore it is not easy to discriminate the heroin use from morphine use 4 5 . The detection of 6-acetylmorphine is recommendable for diagnosis of heroin use because of its relatively long half-life in the body 4 . For accurate diagnosis of a cause of death in an opiate poisoning case the ratio of a free form to a conjugated form becomes important see section 4 of this chapter . In such a case an opiate before free form and after a total amount hydrolysis should be analyzed. The amount of a conjugated form can be calculated by subtracting the amount of a free form from the total amount. By HPLC the simultaneous analysis of free and conjugated forms is possible without any hydrolysis in the near future LC MS may become a main tool for analysis of opiates and their metabolites. However at the present time GC MS is being widely used for opiate analysis. For HPLC analysis of the conjugated forms of opiates the authentic standards of mor-phine-3-glucuronide M-3-G and morphine-6-glucuronide M-6-G are necessary. In . and Europe it is easy to obtain these authentic compounds from commercial sources but the import of these compounds to Japan is strictly controlled easing of import of such compounds should be realized. GC and GC MS analysis .