ACETPHENETIDIN AND PHENACETIN—THEIR RELATIVE PURITY
Until six years ago the chemical product known as phenacetin was patented both as to process and to product. As the patent ran out at that time, anyone, of course, could manufacture it. It was placed in the Pharmacopeia under the name “acetphenetidin.” It is on the market now under both names, “phenacetin” and “acetphenetidin.” The price of the former is five times[130] that of the latter, hence it is rather important to know whether or not one is, in any way, better or purer than the other. The original patentees or manufacturers, the Farbenfabriken of Elberfeld Company, market the product under the name “phenacetin” and also under the official name “acetphenetidin,” the former at about 33 cents an ounce and the latter at about 6 or 7 cents an ounce. Evidently these people believe that acetphenetidin is all right since their price-list says: “Our product is of the highest standard of purity,” and in another place: “On account of the low price of acetphenetidinum, U. S. P., it is especially suitable for the manufacture of medicinal specialties, such as headache powders, etc.” Remember that it is the manufacturers of phenacetin who say this.
The question arose whether or not phenacetin differs from acetphenetidin. If it does, then physicians should know it. An inquiry was addressed to Farbenfabriken of Elberfeld Company and also to Lehn & Fink, two firms which market the product in this country under both names, asking in what respect the two products differ. No answer was received from either firm. With the object of answering the question our chemists have investigated the preparations on the market, both those sold under the name “phenacetin” and those under the official title “acetphenetidin.” The following is a summary of their report:[131]
THE CHEMISTS’ REPORT
Physical Appearance.—All the specimens were found to be fine white crystalline powders, differing somewhat in appearance as follows: Four specimens—Acetphenetidin (Farbenfabriken), Phenacetin (Specimen 1[132]—Farbenfabriken), Phenacetin (Specimen 2[132]—Farbenfabriken) and Acetphenetidin (Squibb)—appeared very much alike, each being a very fine crystalline powder, differing only slightly as to fineness. Five other specimens—Phenacetin (Lehn & Fink), Acetphenetidin, U. S. P. (Lehn & Fink), Acetphenetidin (Merck), and two specimens of Acetphenetidin (Powers-Weightman-Rosengarten), had the same general appearance, each consisting of a fine crystalline powder containing a considerable proportion of large rectangular plates. Three specimens—Acetphenetidin (Mallinckrodt) and two specimens of Acetphenetidin (Powers-Weightman-Rosengarten)—had the same general appearance, being a moderately fine and homogeneous crystalline powder. When examined microscopically with a low-power lens the Mallinckrodt product appeared to consist principally of rectangular prisms and the Powers-Weightman-Rosengarten product to be made up largely of plates.
Identity.—All of the specimens when tested side by side responded to and complied with the identity tests of the United States, British, German, Swiss, Dutch, Swedish, Spanish, and Danish pharmacopeias. The reactions given by the several specimens were all the same, showing no difference in any case.
Melting-Points.—As a further proof of identity and similarity the melting-points of the different specimens were taken and found to be: Acetphenetidin (Farbenfabriken), 134.2 C.; Phenacetin (Specimen 1—Farbenfabriken) 133.7 C.; Phenacetin (Lehn & Fink), 134.7 C.; Acetphenetidin (Lehn & Fink) 134.9 C.; Acetphenetidin (Powers-Weightman-Rosengarten), (1) 134.3 C., (2) 133.6 C., (3) 134.7 C., (4) 134.7 C.; Acetphenetidin (Squibb) 134.2 C.; Acetphenetidin (Merck), 134.8 C., and Acetphenetidin (Mallinckrodt), 134.2 C. The melting-point is given as 135 C. in the British, French and Spanish pharmacopeias, and as 134 to 135 C. in the United States, German, Swiss, Danish, Swedish and Dutch pharmacopeias. Thus all comply with the standard given in our pharmacopeia and most foreign pharmacopeias with two exceptions and those respectively only 0.3 C. and 0.4 C. low.
Absence of Acetanilid.—The absence of acetanilid in all the specimens was indicated by the bromin test of the United States, British, German, Swiss, Dutch, Swedish and Danish pharmacopeias.
Absence of Carbonizable Matter.—The absence of carbonizable matter was shown in all specimens by the sulphuric acid test of the United States, British, German, French, Swiss, Dutch, Swedish and Spanish pharmacopeias.
Water-Soluble Matter.—All specimens when tested for excess of water-soluble matter came well within the limit (0.50 per cent.) set by the French pharmacopeia, the greatest amount being 0.20 per cent.
Ash.—When heated, all the specimens were found to yield practically no ash, the residues from 1 gm. samples weighing in no case more than 0.0004 gm.
Absence of Paraphenetidin.—When tested by the methods of the United States, British, German and French pharmacopeias, the absence of an impurity of paraphenetidin was shown in all specimens, with the exception of one specimen obtained from Powers-Weightman-Rosengarten Co., which gave a positive, though not strong, reaction and two other specimens of the same firm which reacted still more faintly.
TABLE SHOWING RESULTS OF ANALYSES OF VARIOUS SPECIMENS OF ACETPHENETIDIN AND PHENACETIN*
| Name | Physical Appearance | Melting Point (Corr.) C. | Water-Soluble Matter in, per Cent. | Ash, per Cent. | Para- phenetidin, U. S. P. Test† | Para- phenetidin, Swiss Test† |
| Acetphenetidin (Farbenfabriken) (1) | Very fine homogeneous crystalline powder | 134.2 | 0.17 | 0.02 | – | + |
| Phenacetin (Farbenfabriken) | Very fine homogeneous crystalline powder | 133.7 | 0.06 | 0.00 | – | + |
| Phenacetin (Lehn & Fink) | Fine crystalline powder, not uniform | 134.7 | 0.11 | 0.02 | – | + |
| Acetphenetidin (Lehn & Fink) | Fine crystalline powder, not uniform | 134.8 | 0.13 | 0.00 | – | + |
| Acetphenetidin (P. W. R.) (1) | Homogeneous crystalline powder | 134.3 | 0.19 | 0.03 | + | + |
| Acetphenetidin (P. W. R.) (2) | Homogeneous crystalline powder | 134.7 | 0.16 | 0.02 | + | + |
| Acetphenetidin (P. W. R.) (3) | Homogeneous crystalline powder | 134.7 | 0.14 | 0.02 | + | + |
| Acetphenetidin (P. W. R.) (4) | Fine crystalline powder | 133.6 | 0.20 | 0.01 | – | – |
| Acetphenetidin (Squibb) | Fine crystalline powder | 134.3 | 0.19 | 0.00 | – | + |
| Acetphenetidin (Merck) | Fine crystalline powder | 134.8 | 0.15 | 0.03 | – | – |
| Acetphenetidin (Mallinckrodt) | Fine crystalline powder | 134.2 | 0.11 | 0.01 | – | – |
| * In all cases identity was confirmed; acetanilid was absent; carbonizable matter was absent. | ||||||
| † In this column plus indicates presence; minus, absence. | ||||||
While this firm’s product alone gave any reaction whatever when the U. S. P. test for paraphenetidin was applied with the test of the Swiss pharmacopeia, all but Acetphenetidin (Mallinckrodt), Acetphenetidin (Merck) and one specimen of Powers-Weightman-Rosengarten Co. gave positive, though very faint, reactions, indicating that the majority of specimens, including those of the original manufacturer, contain a minute trace of this impurity.
Our findings regarding the product of Powers-Weightman-Rosengarten Co. having been communicated to this firm, their correctness was acknowledged. At the same time the firm wrote: “All that we have on hand now gives negative tests for paraphenetidin, and we believe our present records are correct when we state that all lots which we are supplying now, and have been supplying for some time past, answer all U. S. P. requirements.”
This examination appears to demonstrate that the chemical substance, para-acetphenetidin, whether sold as acetphenetidin, U. S. P., or as phenacetin, is practically identical. The impurity of the product of some of the specimens coming from Powers-Weightman-Rosengarten Co. is too slight to be considered dangerous. Furthermore, a comparison of the “lot numbers” indicates that this firm has been improving its product steadily so that in the future its assurances of an unimpeachable product may be relied on. Inasmuch, therefore, as acetphenetidin complies with all the pharmacopeial requirements as to identity and purity, in just the same way as phenacetin, which sells for as high as five times the price of acetphenetidin, physicians need not hesitate in using the title of the U. S. P. “acetphenetidin” when prescribing this produce.—(From The Journal A. M. A., March 16, 1912.)
Acetphenetidin and Phenacetin
A physician-pharmacist writes: “If a prescription calls for ‘phenacetin,’ should the pharmacist dispense ‘phenacetin-Bayer’—that is, the phenacetin manufactured by the original patentee—or would he be justified in dispensing the official acetphenetidin, manufactured by any reliable chemical or pharmaceutical house?”
Unless the pharmacist happens to know that the physician in writing the prescription desired the Bayer brand, he would be justified in dispensing acetphenetidin, U. S. P. As a general thing, physicians use the word “phenacetin” without intending to prescribe any particular brand or make, simply because they are familiar with this word and are not familiar with the official term “acetphenetidin.” They will doubtless continue to use the term “phenacetin” and we know of no sufficient reason for doing otherwise. During the life of the patent the word “phenacetin” became a familiar one, and the product became generally known by this term. But a coined name for a patented article loses its proprietary character and becomes the common name of the article when the patent expires. In other words, when the patent expires, not only the product but also the name itself becomes common property. This principle has been recognized by the courts. Those who formerly controlled the product and the name “phenacetin” evidently recognized this principle, for they have taken no steps to prosecute a firm in this country which sells the product openly under the name “phenacetin.” It might be added that the preparation is official in most foreign pharmacopeias under the name “phenacetin.” In agreement also with this principle the Council on Pharmacy and Chemistry (The Journal, April 27, p. 1298) lists in New and Nonofficial Remedies such products as “lanolin,” “phenacetin,” “sulphonal” and “trional” as non-proprietary names applied to Adeps lanæ hydrosus, U. S. P., Acetphenetidinum, U. S. P., Sulphonmethanum, U. S. P., and Sulphonethylmethanum, U. S. P., respectively.
In view of these facts—and also bearing in mind the findings of the Association’s Chemical Laboratory (The Journal, March 16, p. 801) that the preparations on the market under the title “acetphenetidin” are of equal quality with the preparations sold under the name “phenacetin”—the pharmacist should recognize that acetphenetidin is identical with phenacetin, is prescribed, provided, of course, that no special brand of phenacetin is ordered.
It is the physician’s privilege, of course, to specify the goods of a particular manufacturer, but in view of the fact brought out above that all brands of this chemical have tested up to the U. S. P. standard, it is placing an unnecessary burden on the pharmacist to require him to have on hand many different brands of one substance. The physician should save this privilege for use when prescribing some product that differs materially in its various forms on the market, as for example in the case of certain fluidextracts.
Physicians will doubtless find that the above comments will interest their local pharmacists. It is of mutual value for physicians to talk these matters over with their pharmacists.—(From The Journal A. M. A., Oct. 5, 1912).