Excretion of Free Morphine in Urine

Because the safe therapeutic dose of morphine in man is small, little quantitative information is available on the excretion of morphine after single doses. Most of the reliable data have been gathered from addicts and is not directly transferable to the individual only occasionally receiving morphine. 

In 1929 Fry et al. (97) found that excretion of morphine by drug addicts was variable and the fraction excreted was unrelated to the absolute amount of the intake. They stabilized 10 patients for 4 days on doses of morphine adequate for comfort, and then studied urinary and fecal excretion for the next 5 days at the stabihzation level of morphine intake. 

Additional data on the excretion of morphine by addicts were provided by Oberst (66). There was very little difference between the average percentage excretion of morphine (5.42 %) and codeine (5.94 %) when administered subcutaneously. During oral administration the percentage of 

The information which had been accumulated up to 1940 indicated that morphine in urine and feces accounted at best for only 10 % of that administered. However, in 1940 Thompson and Gross (96) pointed out that previous workers had estimated free morphine but that in dogs both a free and a combined morphine were present in the urine, and could account for 80-85% of the dose given. Oberst later showed that in addicts a large percentage of morphine was also excreted as a combined form. 

For this series of experiments Oberst (98) developed a colorimetric method in which morphine values as low as 0.14 mg. per 100 ml. urine could be determined readily. The morphine was extracted by an alcohol-chloroform mixture from urine saturated with sodium bicarbonate, purified, and determined colorimetrically after the addition of Fohn-Denis phenol reagent. For combined morphine the urine was acidified with one-fifth of its volume of concentrated hydrochloric acid and boiled under a reflux condenser for 3 hr. After cooling and saturating with sodium bicarbonate, the modified urine was treated in the same manner as for the determination of morphine before hydrolysis. 

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