By MARIE O. GLOVER, A.M., S.B.
Having had occasion to collect and assay samples of tincture of opium from eight of the principal wholesale drug houses of New York, and an equal number of retail drug stores in Boston, it was thought that the results obtained might, perhaps, be interesting, as representing in some degree the strength of this preparation now in the market.
The change in the strength of opium preparations recently made in accordance with the U. S. Pharmacopoeia of 1880 would lead us to expect a greater variation than usual just at this time, although it might be supposed that samples made according to the old standard would bear upon the label some indication of the fact. This was, however, not found to be the case, as the only labels giving any information. in regard to morphia strength were those from wholesale houses, which stated that the laudanum was made according to the U. S. P. 1880, or, in two instances, that it contained 6 grains to the fluidounce.
The method of assay employed was that of Flückiger, modified by E. R. Squibb ("Ephemeris," Vol. I, No. 1, p. 14; "Amer. Jour. Phar.," 1882, p. 244), and it was found necessary to introduce a slight modification of this process, in order to obtain clean, light-colored morphia.
The tincture was measured in every case at 15.6°C. (60°F.), 50 cc. being the amount used in each assay; the weight was also taken. It was then evaporated to 10 grams, 2.5 cc. of alcohol were added, and the mixture stirred, to obtain a uniform solution. This was in most cases impossible, therefore the mixture was poured gradually and with constant stirring into 100 cc. of alcohol, and the beaker covered and set aside until the supernatant fluid had become perfectly clear. The clear fluid was then decanted through a filter, the precipitate washed with alcohol, and the filtrate and washings evaporated until the alcohol was expelled, a little water being added. When the contents of the dish again weighed 10 grams, 2.5 cc. of alcohol were added, and a uniform solution was generally obtained. This was transferred to a small flask with as little additional water as possible, 2.5 cc. more alcohol added, and the flask well shaken. There were now 15 cc. of stronger ether added, the shaking repeated, and lastly 2 cc. of ammonia water (10 p. c. NH3) were added, and the whole shaken until the crystals began to separate, the shaking after this being frequently repeated for half an hour. After standing overnight the ethereal stratum was carefully poured off on to a filter, 10 cc. more ether added, and the contents of the flask rinsed around without shaking. When the ethereal layer had separated, it was poured off through the filter, and the latter washed with 5 cc. of ether, carefully dropped on to the edges from a pipette, and allowed to dry. The remaining contents of the flask were poured on, the flask and filter washed, Using in all only about 10 cc. of wash water. The filter and contents were then dried at 100°C. (212°F.), weighed, the morphia removed, and the weight of the filter taken and subtracted. The result was then calculated to grains to a fluidounce.
The samples were treated as nearly as possible alike, the quantities of ether, alcohol and ammonia being the same, and the time allowed for precipitation about 24 hours in all cases. It was found impossible to assay most of them successfully without the alcoholic precipitation, the morphia obtained being dark-colored and impure, and in 3 out of 4 samples where comparative tests were made, less in amount, the gummy matter separated by the alcohol apparently hindering the precipitation.
The U. S. P. process, as given by Henry B. Parsons, in his interesting report, read before the New York State Pharmaceutical Association ("Weekly Drug News and Am. Pharmacist," June 23, 1883) was tried with 4 of the samples, the results being always lower, by a varying amount (from .2 to .8 grain to the fluidounce), than those obtained by the other process. It appears also that weighing the morphia on balanced filters, when the U. S. P. process is employed, gives a higher result than that obtained by subtracting the weight of the filter on removing the morphia. As the crystals are remarkably clean and easy to remove, the latter would seem to be the more correct method. The increase in weight may possibly be due to the formation of CaCO3 to a greater extent in the pores of the inner filter, which is more exposed to the air during filtration.
The results obtained are as follows:
|No.||Per cent. of Morphia.||Grains of Morphia to the Fluidounce.|
The morphia from each sample was tested for its solubility in lime water ("Ephemeris," Vol. 1, No. 1, p. 18), and in Nos. 8, 10, 11 and 16, which showed a large amount of insoluble matter (the others containing traces merely), a correction was made for this, the amount being determined by collecting the insoluble substance (narcotine ?) from about 0.5 gram on a balanced filter, drying and weighing. The use here of the balanced filter cannot well be avoided, as the precipitate is of such a nature that it would not be possible to remove it, but it is open to the same objection as above, and the amount of impurity thus found is doubtless somewhat high. Before making the reduction the figures stood: No. 8, 5.63 grains, No. 10, 4.44 grains, No. 11, 4.89 grains, No. 16, 5.72 grains, to the fluidounce.
Nos. 1, 2, 6, 8, 14, 16 and 17 are all probably intended to answer the requirements of the U. S. P., 1880. A sample of laudanum (No. 15) made from 15 per cent. opium, according to the U. S. P., substituting 40 parts each of alcohol and water for 4 as directed, yielded, after making the subtraction for impurities insoluble in lime water, only 5.70 grains to the fluidounce, 6.03 being the amount obtained before correction.
Nos. 3, 7, 10 and 11 would fulfil the requirements of the U. S. P., 1870, according to which the minimum strength would be 3.75 grains to the fluidounce. Nos. 9 and 13 are perhaps intended to conform to this.
Nos. 4, 5 and 12 agree neither with the old strength nor with the new, but come within the limits (2-3 to 3-3 grains to the fluidounce) assigned by Mr. Parsons to laudanums probably made from moist opium.
Thus, of the 16 samples of tincture of opium we have 7 answering nearly or quite the requirements of the U. S. P., 1880, 4 meeting those of the U. S. P., 1870, 2 somewhat below this standard, and 3 containing such a small percentage of morphia that they are open to the suspicion of having been intentionally made of low morphia strength.
In every case, however, where the label contained the letters U. S. P., or the statement that the laudanum was made according to the U. S. P., 1880, it was found to contain between 5 and 6 grains of morphia to the fluidounce.
The number of samples is not large, and they were obtained only from New York and Boston, therefore it is hardly safe to draw general conclusions from the assays; but as these samples were received in June, 1883, at least seven months later than those assayed by Mr. Parsons, and after sufficient time had elapsed for the new standard to be adopted, it may, perhaps, not be quite useless to give the results.
Laboratory of Dr. E. R. Squibb,
Brooklyn, N. Y., August 31, 1883.
The American Journal of Pharmacy, Vol. 55, 1883, was edited by John M. Maisch.