D. W. Chasar' ond G. B. toth2 University o f Pittsburgh at Johnstown Johnstown, Pennsylvania 15904
T hin-Layer Chromatography of Darvon
A casual glance through any recent issue of this J o u m l reveals that more and more undergraduate laboratory experiments are being oriented toward drugs (1-5). Our organic laboratory experiments are also tending in that direction (6). I n light of the new interests in Darvon (7), we decided that the thin-layer analysis of Damon drugs would be appropriate. Damon Compound-65, a n effective analgesic, consists of four components (8): caffeine (I), phenacetin (11). aspirin (Im, and propoxyphene hydrochloride (IV), itself known as Damon. Other analgesic formulations containing Darvon are also available. Darvon is an odorless white crystalline powder with a bitter taste and is freely soluble in water. Chemically, it is a-(+)-4-(dimethylamino)-3methyl-1,2-diphenyl-2-butanol propionate hydrochloride. Neman (2) has suggested that Darvon gives a n "interesting chromatogram" when analyzed on standard size (20 cm long) tlc plates. However, due to the high cost of these plates and our dwindling budgets, we developed conditions for Damon analysis on coated microscope slides. A few problems were encountered in finding ideal conditions for complete separation on microscope slides. I n many eluents, aspirin and caffeine have nearly identical Rt values, leaving some ambiguity as to what's present. This problem was circumvented by two different procedures. A change in eluent which separated aspirin or caffeine from the remaining three components was used, or prior extraction of the aspirin from the mixture followed by tlc analysis afforded a reasonable solution. We preferred the latter procedure since it extended the already learned technique of extraction. Iodine vapor was a poor means of visualization since i t gave long brown streaks instead of individual spots, presumably due to the very similar R, values of the compounds. This problem was avoided by using a fluorescein spray with uv light visualization. A third problem with the experiment is that Darvon and its formulations are prescription drugs. Neman (2) circumvented this problem by obtaining a drug license. However, we overcame the problem by having the students bring in Darvon capsules from their own medicine cabinets. This also cut down our costs a s well as showing the students that the samples they used are not "fixed." Associated with this solution is the problem that one cannot get pure propoxyphene HCI, the main component of Darvon-65 a s a reference sample. However, the other components are readily available. In fact, in our experiments, the students have already isolated caffeine from No-Doz or tea and have synthesized aspirin. Thus, two of the reference compounds which they need they have isolated themselves. Experimental
TIC plates were prepared by dipping two miemscope slides, back to back, into a slurry of 42 g of Silica GeP in 100 ml of 2:l ehlorafom-methanol.No activation of the plates was necessary. The finely powdered contents of one Dawon capsule and 3 ml of concentrated ammonia are thoroughly mixed in a small centrifuge tube and extracted with 3 ml of chloroform. The two phases are thoroughly mixed (4) by placing a spatula in the tube and rapidly rotating the shank of the spatula between the thumb and index finger. The phases are allowed to separate and the lower
chloroform layer, absent of aspirin, is transferred with a dropping pipet to a clean vial. To recover the aspirin, the remaining ammonia solution is neutralized with 10 M HCI end adjusted until slightly acidic to litmus paper. This solution is then extracted with 3 ml of chloroform as before and the bottom layer is removed. These two chloroform solutions should contain all the components present in the Darvon capsule. A few microliters of each of these solutions are ehromatographed on the coated miemscope slides in the usual manner using 80:20 acetone-chlorofom as the eluent. After the plate has been dried, it is sprayed with a fluorescein solution4 and visualized under uv (254 nm) light. Aspirin appears as a fluorescent light blue spot, pmpmyphene as a fluorescent yellow green spot and caffeine and phenacetin as dark bmwn spots. Aspirin, caffeine, and phenacetin can he identified by comparing authentic samples on tlc against the Darvon capsule contents. Typical Rt . values are: propoxyphene, 0.2; caffein, 0.4; aspirin, 0.4; phenaeetin, 0.7. Alternate eluents which can be used to identify aspirin without going through the extraction process are (by percent): ethanol (5), dioxane (40), benzene (50). ammonia (5) or ethyl acetate (60), benzene (35). ammonia (5). Interesting changes in Rt values occur. 0
II
Literature Cited (11 Moye,A.L., J.CHEM.EDUC.,49.170!1972). (21 Neman, R.L., J . CHEM.EDUC., 19,834 (19721. (31 Krantz,A.and Jessitis,R.G.,J C H E M E D U C . , JO,l6(19731. (I1 PavlL, J. W.. J.CHEM.EDUC..59.134(19131. (51 Bmm, D. G. and Friedman. L . 8.. J. CHEM. EDUC., 50.214 119731. (61 Ch8aar.D. W. andT0th.C. B., J. CHEMEDUC.. 51,22!1910. (11 "Methadone Subsluute Tested," The Pittsburgh Prpss. Sunday. M a y TI, 1913. p. C-28.
(81 "Phmicianr' Den* Reference," 26th Ed., Medical Economies Co.. Oradell, N. J.. 1972. D. 844.
1 To whom inquiries should be addressed. The authors acknowledge the financial support of this work by the University of Pittsburgh at Johnstown. cnderfladuar~research participant 3 SilireGel7 G obtained from.1.T. Hakrr Chemncal Cumpan?. 4 Preoared by dissolving 0.2 . a of fluorescein in 1M ml vf 95% &hand.
Volume51, Number 7. July 1974
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