FREE AND BOUND MORPHINE IN THE URINE OF MORPHINE ADDICTS

It has been known since the early observations of Kauzmann (1), Vogt (2), Jacques (3), and Faust (4) that morphine is eliminated in the urine and feces of human addicts, but its excretion was not studied quantitatively until 1929 when Fry, Light, Torrance, and Wolff (5) reported their work on the excretion of morphine by human addicts. They found that the daily administration of 15 (0.975 grams), 30 (1.950 grams), and 60 (3.900 grams) grains morphine sulfate resulted in an average elimination of 8.7, 9.8 and 10.7 per cent respec-tively. The percentage excretion was not affected by the “degree ” of the addiction, by the quantity of drug administered, or by the duration of addiction. Their method of extracting the alkaloid from urine and its subsequent determination was developed by Balls and Wolff (6). The morphine in the final extract was precipitated by silicotungstic acid and the amount deter-mined gravimetrically. When the quantity of morphine in the final extract was less than 10 mgm., it was estimated colorimetrically by the diazo-reaction (7, 8). In so far as the daily dosage range was from 15 to 60 grains (0.975 to 3.900 grams) of morphine’sulfate a considerable amount of the drug would be present in a small volume of urine, consequently fairly reliable results could be obtained by the method used. However, for lower dosage levels ranging between 1 and 5 grains (0.065 to 0.325 grams) per day, the amount excreted in the urine of addicts would be too low for satisfactory analyses by their method. Pierce and Plant’s procedure (9) was an improvement, but it too was not entirely satisfactory for the analysis of human urine having very low morphine concentrations. Later Oberst (10) developed a colon-metric method in which morphine values as low as 0.1 mgm. per 70 ml. urine could be determined readily. This method was further supplemented by a nephelometric method when morphine concentrations in a sample were less than 0.1 mgm. In these methods it has been assumed that all of the morphine in the urine is present as an alkaloidal salt which can readily be liberated as the free base after saturating the urine with sodium bicarbonate. The morphine not foun