Hydrolysis diamorphine

It is a prodrug with no opioid activity itself. All its pharmacological activity derives from hydrolysis to monoacetylmorphine (MAM) and then to morphine in the plasma and tissues. Diamorphine also... 

Therapeutic Concentration. Because of its rapid hydrolysis, diamorphine is difficult to detect in plasma. Morphine plasma concentrations are usually in the range 0.01 to 0.07 pg/ml. Diamorphine was detected in blood 2 minutes after an intravenous dose of 4 to 5 mg given to 4 subjects, but declined to a blood concentration of less than 0.01 pg/ml within 10 to 15 minutes (C. E. Inturrisi et al.. New Engl. J. Med., 1984, 310,1213-1217). 

Disposition in the Body. 6-Monoacetylmorphine is the first hydrolysis product of diamorphine. It is further metabolised to morphine. 

Methanol is a good universal solvent, but may result in the rapid hydrolysis of trace amounts of diamorphine to monoacetylmorphine and morphine itself. As such, where possible, it should be avoided for heroin analysis, in particular the analysis of trace samples of heroin. Chloroform is an ideal solvent, but will rapidly evaporate from the swab. With care, however, it can be used since there are not the hydrolysis problems associated with methanol. 

First, if, for example, a powder is to be examined, then it should be freely soluble in the solvent chosen for injection into the chromatographic system. Secondly, the solvent should be fully miscible with the mobile phase. For these reasons, methanol is frequently chosen for heroin analysis, although the drug should not be left in this solvent for long periods because of the risk of hydrolysis of some of its components, e.g. monoacetylmorphine and diamorphine. 

Diamorphine (or heroin) is the diacetyl derivative of morphine and, like morphine, is used as a narcotic analgesic (Figure 8.21). The two acetyl groups are important for two reasons first, they render the molecule more lipophilic (increasing the partition coefficient), which means that diamorphine is absorbed into the central nervous system more rapidly than is morphine, and in turn results in a faster onset of action than for morphine (and, sadly, makes the compound a favourite with addicts). The second aspect of the two acetyl groups is that they are susceptible to hydrolysis, to yield morphine and two molecules of acetic acid (Figure 8.21). 

In the determination of diamorphine, terpin hydrate cannot be eliminated by preliminary extraction with solvent or by hydrolysis with acid however, it is mainly volatilised in the evaporation of the solvent extracts. 

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