G. F. Pisani I. T. I. S. for Industrial Chemists "L. CASALE"
Torlno, Italy
I
Quantitative Analysis of APC Tablets An easy experimental method based on the use of ion exchange resins
The ion exchange resins are useful in the separation of acetylsalicylic acid (aspirin) from phenacetin and caffein in APC tablets. The two last substances are organic bases; therefore, an anionic exchanger will retain acetyl~alicylicacid much more strongly than phenacetin and caffein. The aspirin can be eluted from the resin with hydrochloric acid a t the proper concentration; phenacetin and caffein, on the contrary, can be eluted with water. The two organic bases, in the eluate, can be measured by the spectrophotometric method of simultaneous determination; for aspirin a calibration curve is useful, obtained by plotting the absorbance versus concentration of a series of standard solutions of acetylsalicylic acid dissolved in HCI a t the same molaritv used for the elution. In ltaly the iirnulraneous presence of three substanres A (acetylialicylic acid) P (phenacetin) C icaffeinl in tahlets is unusual; however, the coupling (,f two substances (A-C;P-C; . . . I is common. Thereforc it is ~ossihleto extend rhis qunntititive method to many medical tablets with a preliminary oualitative analvsis by tlc.' In this way, the right combination can be identifieh and, by the ion exLhange resins method, it is then ~ussihleto determine the perrentage of components in the tablets. Before quantitative analysis, ahsorhance spectra of the components of APC are determined to identify the maximum absorbance useful in the analysis; moreover, if an automatic fractions collector is available, the students may become skillful in elution from ion exchange resins testing, for example, with a linear elution gradient, the most useful eluent (in fact, to reduce the time of the ex~erimentwhile maintaining its accuracy, it is impo&t that the volume of eluate not exceed 100-200 ml). In our case we take as absorbance maximum for phenacetin A = 243 nm; while for acetylsalicylic acid and caffein the maximum is a t A = 275 nm. The specific absorhances at 275 nm and at 243 nm, for phenacetin and caffein, are also calculated for a simultaneous determination; the table gives the experimental values expressed as absorbances of solution obtained by dissolving 1mg of substance in 11. ~~~~
~~~
Absorbance of Solution (1 mg in 1 I ) Substance
243 nrn
275 nm
Phenacetin
0.0596 0.0101
0.0098 0.0462
caffein
and continues in glass column. The ratio of volumes of NaOH and HCI solutions to the volume of resin bed is in the range of 4:l. I t is advisable to see that the maximum in absorbance of the last hydrochloric acid washing eluate a t 275 nm not exceed 0.015-0.030. Finally, water washings of the resin must be continued until the pH of the eluate and the pH of water in the reservoir are coincident and the ahsorbances at 275 and 243 nm do not exceed 0.015-0.030. The resin bed, prepared in this way, is then kept in a stoppered plastic bottle with clear water. It is advisable to prepare a volume of resin sufficient for manv exneriments. since the analvtical orecision and accuracy of the next analysis is, in this ,way, guaranteed. Considering the low cross-linkage of the resin that u,e used, the swelling in water was remarkahle. Class Column for Chromotocrauh>: height = 0.2 rn; i.d. = 0.01 m; the coh& is connectedto r&ervo; (namely a funnel separator) by means of a polyethylene tube (Fig. 1). Automatic Fractions Collector. e
.
a
Experimental
A resin bed, 0.1 m high, is prepared in the column. Three water solutions are prepared, one with 0.25 g of pure acetylsalicylic acid, a second with 1g of phenacetin, and a third with 4 g of caffein in 11. Each solution is treated as follows: 10 ml 1
Lieu, Van T.,J. CHEM. EDUC.,48,478 (1971).
Chromatographic Equipment
Ion Exchange Resin DOWEX 1
x 1, 50-100 mesh, as C1'; the resin Figure 1. Apparatus for chromatography in column and automatic collection of eluate fractions.
is prepared by putting i t in 2 M sodium hydroxide, washing i t with water and, finally, with 2 M hydrochloric acid. Each of the preceding operations begins in "batch"
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0
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50
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I
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1 0
ml
150
ELUATE VOLUME
Figure 2. Elution diagram of acetylsalicylic acid by 0.05 MHCi.
Volume 53. Number 11, November 1976 / 733
of solution is passed through the resin bed, then the elution with water (2.5 mllmin velocity) is performed, and 200 ml of eluate are collected in 20 fractions of 10 ml. For each fraction the spectrophotometric absorbance is examined a t the A,, proper of the substance that is used. It is observed that phenacetin and caffein are completely eluted from the resin after the first 6&100 ml of water elution; the acetylsalicylic acid, however, (Fig. 2) is not eluted by water from the resin, hut it iseluted byabout IOOmlof O.06MHCl (2.5 mllmin). At this point the medicinal tablets can he analyzed. A water solution is prepared containing a known number of tablets so that the concentrations of A, P, and C are under the limita of their solubility. Then 5 or 10 ml (exactly measured) of the solution are passed through anew resin bed having the same
734 / Journal of Chemical Education
height and diameter mentioned above. The water elution is made, and the solution passed through the resin and water eluate is completely collected in the same graduate cylinder until the volume reaches 150 ml. This water solution is used to determine phenacetin and caffein (through a calibration curve, if only one substance is present, or by means of the simultaneous determination method, if both substances are present). Finally, an elution by 0.05 M HCI is made until the eluate volume reaches 150 ml. This hydrochloric solution provides the acetylsalicylic acid concentration, through the calibration curve. I t must be emphasized that a variation of the elution velocity between 2.5-3 rnllmin is not important for the accuracy of the analysis.
