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When such a collective subject has been the business of one lifetime, and becomes the expectancy of two other commencing lives educated with special reference to the subject, it does not seem irrational to hope that information may be given which may be interesting and useful to the medical and pharmaceutical professions, since the subject is the very foundation upon which the utility of these professions to mankind depends. The younger associates in this undertaking may, perhaps, at first do but little of the writing, but they will do much of the work upon which the writing is to be based.

To the professions of Medicine and Pharmacy, then, whatever may be here offered is respectfully dedicated by the writer and his two

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sons.

EDWARD R. SQUIBB.

BROOKLYN, January, 1882.

THE STRENGTH OF OPIUM AND THE NEW

PHARMACOPEIA.

When, in 1848, a law was passed by Congress “ To prevent the importation of adulterated and spurious drugs and medicines," a careful examination of authorities seeins to have been made in order to fix upon a strength below which Opium should not be admitted into the country, and this minimum strength was fixed at 9 per cent. . of pure morphia. From that time to the present, this 9 per cent. has been the rule of downward limit for all the United States Custom House examiners, and Opium below that strength has never been lawfully admitted to entry in any Custom House of this country. As the loss of water in drying commercial Opium varies between 17 and 23 per cent., the average loss falls at about 20 per cent., and this is proved to be true by a large experience with the better grades of the drug. Hence Opiums which in the moist chemical condition yield 9 per cent. of pure morphia, when dried and powdered would give 11.25 per cent. pure morphia.

The Pharmacopeia of 1850 is silent upon the strength of its Opium ; but that of 1860 prescribes that the officinal Opium shall not contain less than 7 per cent. of morphia. This was a curious mistake to make by so high an authority, for if no Opium could lawfully get into the country which contained less than 9 per cent., it had the inferential force of an invitation to unlawfulimportations.

The Pharmacopeia of 1870 defines that Opium, when dried at 212° F., until it ceases to lose weight, should contain at least 10 per cent. of morphia. This was an improvement in degree on the ruling of 1860, but it was still behind the lawful standard by 1.25 per cent. Now it becomes very important to see what the Pharmacopæia of 1880 will do, since the proposed law of Congress to prevent the adulteration of food and medicine, which, when passed, will become the general model for State laws, makes the Pharmacopæia the only standard. This will then take the place of the present Custom House law, and as all Opium must pass through the Custom House, the law which applies there will be of primary importance. If the Pharmacopæia standard should remain as at present, and the general adulteration law be passed affirming the Pharmacopeia as its standard for all medicines which it contains, then the Custom House examiners will have to abandon their 9 per cent. standard and fall back to 8 per cent. As the average unadulterated Opium of the past thirty years has not fallen off in strength, but, on the contrary, many of the inferior grades of thirty years ago, such as Constantinople Opium, for example, have so improved, that now they are among the finest Opiums, this would be a serious misfortune to the true interests of medicine in this important article. Standard authorities with much unanimity give the medium dose of Opium as 1grain=.065 gramme, and a corresponding dose of salts of morphia as about •2 grain=.013 gramme. The salts of morphia in common use, the sulphate for example, contain about 80 per cent. of pure morphia. This makes the medium dose of pure morphia, -equivalent to two-tenth's of a grain of sulphate,-16 grain=.0104 gramme. Now if the medium dose of Opium and the medium dose of morphia be compared in equivalence, that is, if one grain of Opium produces about the same effect as .16 grain of morphia, then the Opium must contain about 16 per cent. of morphia. It is highly probable, then, from this and from other considerations of past therapeutical experience, that the authorities who have compiled the therapeutic standards of doses from actual recorded experience have based their statement of dose upon Opium of 16 per cent. strength. It is true that these same authorities give the average percentage strength of good Opium as about 12 to 13 per cent. ; but the processes of assay to which these refer are all faulty, and have been so much improved of late years, that it becomes almost certain the older processes. failed to give account of all the contained morphia. Hence it may be regarded as extremely probable that the Opium upon which the therapeutic experience of the past based the medium dose was an Opium which really contained 16 per cent. of pure morphia, or within say 1 per cent. of this on either side of this number—that is, 14 to 17 per cent. Then it follows that if the new Pharmacopeia should adopt a standardized powdered Opium, which would represent the recorded therapeutic uses and doses of the drug, it should contain 14 to 17 per cent. of morphia.

In an effort to find out what strength of Opium was supplied to the markets as a medicinal agent, the writer has collected the assays of 8 lots of moist commercial Opium, all of the crop of 1879 and 1880. These 8 lots comprise 191 cases, and the lots were severally 10, 10, 7, 5, 10, 50, 29 and 70 cases. The minimum yield was 9.6 per cent, and the maximum 11.1 per cent., and the average was 10.25 per cent., for the 191 cases. This being all old Opium, would give a minimum loss in drying and powdering for medicinal uses. Say that it would lose the minimum of 17 per cent., then the powdered Opium from this would contain 12.35 per cent. of pure morphia. But inuch, if not all of this Opium, was below the average market grade for medicinal uses, and was sold at low prices to makers of morphia salts. None of it, or at least very little of it, would have brought the current prices of prime Smyrna Opium, and some was so poor-looking that it would not have been sold at all without being previously assayed. Leaving out the poorest lot of 50 cases, which contained 9.6 per cent. of morphia, the average would be 10,5 per cent., or, if dried and powdered, the 141 cases would average not less than 12.65 per cent. And the 50 cases of 9.6 per cent. Opium, taken alone, would yield a powdered Opium of 11.6 per cent. morphia strength.

When Opium is objected to on account of its poor appearance, either in the New York market or the Custom House, the writer occasionally serves as referee. Two lots, one of 28 cases, and the other of 7 cases, gave an average for the 35 cases of 10.3 per cent., equal to 12.8 per cent. if dried and powdered. Another lot of 3 cases, very old and dry, gave an average of 12 per cent., equal to 14 per cent. if dried and powdered. Another lot of one case gave 12.7

per cent., equal to 15 per cent., if dried and powdered.

This aggregate of 230 cases of Opium fairly represents the worst Opium that is knowingly admitted into this country under the operation of the present law, which says no Opium shall come in which has less than 9 per cent. of pure morphia, and the average of the whole 230 cases is 10.29 per cent., equal to 12.45 per cent. if dried and powdered.

It was next very desirable to know the morphia strength of the better or ordinary grades of Opium, or that which is generally supplied to dispensing pharmacists, and which thus comes more within the scope of the Pharmacopoeia. First the writer, and then an unknown messenger bought "a quarter of a pound of the best powdered Opium for dispensing,” from eight of the largest wholesale drug houses of Philadelphia and New York, if not the largest in the country. These eight firms probably supply the powdered Opium for prescription use and for preparations of Opium, to 75 or 80 per cent. of the pharmacists of New York, Brooklyn, Jersey City and neighboring towns and villages, or over two millions of population, to say nothing of their distributing business all over the United States. These eight samples were carefully assayed by a process, to be given hereafter, and yielded, respectively, 15.1, 14.5, 14.4, 14.3, 14.0, 13.9, 12.5 and 9.5 per cent. of pure morphia. The last sample, the 9.5 per cent., was badly adulterated with dextrine or some form of gum. And next to the last, or the 12.5 per cent., bore the label and seal of Merck, of Darmstadt. This sample also seemed to have some gummy admixture which rendered the assay process difficult and tedious; but the proportion was not larger than would be necessary to standardize a richer Opium, and it is presumed from the high character 'of this manufacturer that he sells a standardized powdered Opium of uniform strength. The last, 9.5 per cent. sample, had much the same appearance as that of Merck, and differed from all the others, so that it is not improbable that it was imported in powder.

As the firms who dispensed these last two samples do a much smaller business than any of the others, and as the samples are exceptional, they might be left out. But as the original design was to take the whole eight houses, they are retained in the average. This average is 13,52 per cent. of pure morphia. The writer himself supplies a considerable quantity of powdered Opium, which, if added, would not reduce the average, but which is excluded from considcration in this paper. It may be, therefore, pretty fairly represented that the powdered Opium of this market is uniformly of the same grade or kind, and that that grade does not vary more than 1 per cent. between the extremes of morphia strength, and that that strength is not far from 14 per cent. Calculating this 14 per cent. powder back to the moist condition, it indicates for the moist commercial drug as imported, a morphia strength of 11.2 per cent. for this grade of Opium, or about '9 per cent. higher than the average

of the 230 cases of lower grade as given above, and all are well within the 9 per cent. minimum limit set by law, and the whole result is an excellent illustration of the advantages of the law, and also of the inutility of the Pharmacopeia setting a standard which is below the law, as it did both in 1860 and 1870, but which it should never again do. If the Pharmacopeia should still adhere to its low minimum, and if the law now before Congress should pass, making the Pharmacopæia its standard, this will repeal the present law, which has served so well, and will reduce the minimum to 8 per cent. instead of 9 per cent., and will place the Pharmacopæia in the undesirable position of leading downward instead of upward. Should the Pharmacopæia for 1880 adhere to the present minimum of 8 per cent.=10 per cent. for dried Opium, and should the bill to prevent adulterations, now before Congress, become a law, and thus repeal the present 9 per cent. law; and should the new Pharmacopeia adopt a standardized Opium with a standard so low as 10 per cent., it would not only materially disturb, but would revolutionize, the preparations of Opium. The medium dose of the tincture and deodorized tincture equal to a grain of Opium is 13 minims or 25 drops; but should these preparations be made from powdered Opium of ten per cent., this dose will be equivalent to only •11 grain of morphia, when, as above shown, the stated medium dose for the morphia in morphia salt is 16 grains, or nearly 50 per cent. more. But when these tinctures are made from the average of powdered Opiums now being supplied in the market-namely, 13,5 per cent. -their medium dose becomes •14 grain of morphia, or much more nearly equal to the authoritative dose of the morphia salts. If a powdered Opium of 14 to 14,5 per cent. be taken for these preparations, then the authoritative doses of the tinctures and of the salts of morphia approach still closer to their proper equivalency, though the morphia in the dose of tincture is still only •141 against .16. But as the other sedative alkaloids of the tinctures must be taken into account, the total sedative and anodyne effect may be estimated as high as .15 against.16. It seems plainly deducible from these consid. erations that the strength of powdered Opium upon which the doses of the preparations are based and adjusted is about 15 per cent., and such Opium can always be had in the general market. And not only that, but such powdered Opium is now very generally supplied, so that these tinctures containing •15 grain of morphia to the medium dose are now in very general use, and the current therapeutic practice and experience must be largely based upon this strength. A

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