ISSN 00360244, Russian Journal of Physical Chemistry A, 2013, Vol. 87, No. 13, pp. 2191–2194. © Pleiades Publishing, Ltd., 2013.
PHYSICAL CHEMISTRY OF SOLUTIONS
Synergic Effects in the Extraction of Paracetamol from Aqueous NaCl Solution by the Binary Mixtures of Diethyl Ether and Low Molecular Weight Primary Alcohols1 ˆ
G. M. Nikolic´ a, J. V. Z ivkovic´ b, D. S. Atanaskovic´ b, and M. G. Nikolic´ c a
Department of Chemistry, Faculty of Medicine, University of Niš, 18000 Niš, Serbia of Pharmacy, Faculty of Medicine, University of Niš, 18000 Niš, Serbia c Department of Chemistry, Faculty of Sciences and Mathematics, University of Niš, 18000 Niš, Serbia email:
[email protected] bDepartment
Received December 21, 2012
Abstract—Liquidliquid extraction of paracetamol from aqueous NaCl solutions was performed with diethyl ether, 1propanol, 1butanol, isobutanol, 1pentanol, and binary mixtures diethyl ether/1propanol, diethyl ether/1butanol, and diethyl ether/isobutanol. Among the pure solvents investigated in this study best extrac tion efficacy was obtained with 1butanol. Synergic effects in the extraction with binary mixtures was inves tigated and compared with some other systems used for the extraction of poorly extractable compounds. Results obtained in this study may be of both fundamental and practical importance. Keywords: paracetamol, liquidliquid extraction, synergism. DOI: 10.1134/S0036024413130189 1
INTRODUCTION
Paracetamol (Nacetylpaminophenol, acetami nophen) is one of the most widely used analgesic and antipyretic drugs. Monitoring of paracetamol and other analgesic drugs in various samples is of great importance since their misuse may lead to serious toxic effects [1]. Determination of paracetamol may be performed by various analytical techniques and liq uidliquid extraction is often included during the sam ple preparation for analysis [2]. For that purpose diethyl ether alone [2] or in combination with some other organic solvents (e.g., dichloromethane [3]) is frequently used. However, paracetamol, like many other phenolic and acidic organic compounds, is poorly extracted from aqueous media with common organic solvents, including diethyl ether. In such cases the problem of poor extractability may be overcomed by saltingout [4, 5] or/and extraction with binary organic solvent mixtures (synergism) which is probably best described for the case of phenol [6–8]. There are also literature data describing synergism in the extraction of pharma cologically and biologically important compounds like antibiotics [9], ascorbic and nicotinic acids [10], and amino acids [11]. The detailed study of extraction pro cess is very important for both fundamental and prac tical purposes [12] and we already performed the study of various inorganic salts influence on the extraction of 1 The article is published in the original.
paracetamol from aqueous solution by the diethyl ether/1butanol solvent mixture [13]. In this paper we present the results of the study of synergic effects in the extraction of paracetamol from aqueous NaCl solu tion by the binary mixtures of diethyl ether and low molecular weight primary alcohols. EXPERIMENTAL Paracetamol (SigmaAldrich, France; >98% purity) was used without further purification. The sol vents used in this study; diethyl ether (DEE), 1pro panol (1PrOH), 1butanol (1BuOH), isobutanol (2 methyl1propanol, iBuOH), and 1pentanol (1PeOH); were purchased from Merck (Germany) and were used as received. Paracetamol solution (0.01 mol dm–3) in aqueous NaCl (4 mol dm–3) was prepared just before extraction by dissolving exactly weighted amount of substance. No specific adjustment of pH value was performed since preliminary investi gations showed that pH values in the range from 2 to neutral had no effect on the extraction efficiency of paracetamol. Extraction of paracetamol with pure organic solvents or binary solvent mixtures was done manually by the shakeflask method and UV absor bance of aqueous phase was measured at 244 nm before and after each extraction. All extractions were performed at room temperature (22 ± 1°C) in dupli
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RESULTS AND DISCUSSION Distribution ratios for the extraction of paraceta mol from aqueous NaCl solution were first measured for pure solvents. The D value for the extraction with DEE was 0.79. The D values for the extractions from the aqueous solution of NaCl (4 mol dm–3) with vari ous primary alcohols are given below:
D 40 2 30
1
20
1PrOH 17.65
3 10
0
0.2
0.4
0.6
0.8
1.0 x
(1) Dependence of D values (Dmix) on the composition for the binary mixtures (x) of DEE and 1PrOH, (2) 1BuOH, and (3) iBuOH (crosses) in the extraction of paracetamol from aqueous NaCl solutions. Dashed lines correspond to the dependences of theoretically predicted D values (Dadd) on the binary mixtures compositions.
cate and average absorbance values were used for cal culations. Spectrophotometric measurements were per formed by using Evolution 60 UVVis scanning spec trophotometer (Thermo Scientific, USA). Quartz cells (1.0 cm) were used for absorbance measurements with the aqueous NaCl solution (4 mol dm–3) as a blank. Distribution ratio (D) of paracetamol was cal culated by using the equation
D=
A0 − A Vaq , × A Vorg
(1)
where A0 and A were absorbances of the aqueous phases before and after extraction, and Vaq and Vorg were the volumes of aqueous and organic phase, respectively. Synergic effect in the extraction of parac etamol with binary solvent mixtures was quantified by calculating the synergic coefficient, Kc, according to the equation Kc = log(Dmix/Dadd),
(2)
where Dmix represented experimental (Eq. (1)) and Dadd theoretically predicted distribution ratio values, respectively [10, 13]. Theoretically predicted distribu tion ratio was calculated as Dadd = D1 × x1 + D2 × (1 – x1),
(3)
where D1 and D2 represented distribution ratios of paracetamol for pure solvents, and x1 was mole frac tion of one pure solvent in binary mixture.
1BuOH 31.59
iBuOH 16.92
1PeOH 21.43
Primary alcohols showed good performances in the extraction of many poorly extractable substances especially under saltingout conditions [5] or/and in combination with other solvents [9–11, 14, 15] both in terms of satisfactory high D values and good phase sep aration. Unlike 1PrOH which is completely miscible with water at room temperature and can be used for the extraction from aqueous solutions only in combi nation with saltingout agents, other alcohols used in this study are only partially miscible with water but their extraction performance is largely improved under saltingout conditions [16]. This was demonstrated for various chloride salts in the extraction of paracetamol with DEE/1BuOH binary mixtures when much higher D values were obtained in comparison with val ues for the extraction from the aqueous solutions con taining no salt [13]. Decreased extraction efficacy of 1PeOH in com parison to 1BuOH has already been noted for aro matic αamino acids [14] and the decrease of extrac tion efficacy of nalkanols with increase of the number of carbon atoms was detected in the extraction of ace tic acid [15]. It seems that 1BuOH has optimal bal ance of the hydrophobic and hydrophilic parts of the molecule for the extraction of poorly extractable sub stances. Synergic effect in the extraction of paracetamol from aqueous NaCl solution was investigated for the binary mixtures of DEE with 1PrOH, 1BuOH, and iBuOH. Although some preliminary results were obtained for 1PeOH extraction, detailed investiga tion of the extraction with DEE/1PeOH mixture was not performed because extraction with 1PeOH was significantly less efficient than with 1BuOH. Also the primary goal of this study was to investigate the behav ior of water miscible or partly miscible primary alco hols in the extraction of paracetamol under saltingout conditions in combination with DEE. The depen dence of D values on the composition of binary mix tures (x) is shown in figure. As can be seen from the figure for all three pairs of solvents investigated in this study positive synergic effect (larger Dmix in comparison to Dadd) was observed in the whole composition range of binary mixtures. For each pair of solvents highest D value was obtained for the mixture containing an excess of alcohol which was expected since D values for alcohols are much
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SYNERGIC EFFECTS IN THE EXTRACTION OF PARACETAMOL Distribution rate (Dmix and Dadd) and synergic coefficient (Kc) values for the extraction of paracetamol with binary mixtures of diethyl ether and alcohols used in this study φ
x
0.2 0.4 0.6 0.8
0.258 0.484 0.676 0.848
0.2 0.4 0.6 0.8
0.222 0.433 0.632 0.821
0.2 0.4 0.6 0.8
0.220 0.430 0.629 0.819
Dmix 1PrOH 7.98 18.17 23.76 21.53 1BuOH 9.95 23.36 35.28 36.04 iBuOH 7.03 15.50 19.55 18.37
Dadd
Kc
5.15 8.96 12.19 15.09
0.190 0.307 0.290 0.154
7.60 14.11 20.24 26.07
0.117 0.219 0.241 0.141
4.32 7.71 10.92 13.99
0.212 0.303 0.253 0.118
higher than for DEE. However, higher D values in each case were obtained with mixtures containing some fraction of DEE than with pure alcohol (table) which means that only a combination of Hbond donor component (alcohol) and Hbond acceptor component (DEE) enables optimal extraction of paracetamol. Similar behavior was observed for some other poorly extractable compounds [9–11, 15]. Calculated values of synergic coefficients (Kc) for binary mixtures investigated in this study together with observed (Dmix) and calculated (Dadd) distribution rate values are all given in table. Highest D values were obtained for the mixtures of DEE with 1BuOH (table) which is in accordance with the fact that for pure solvents best extraction effi cacy was observed for 1BuOH. Maximal D value for this mixture was obtained for DEE volume fraction (φ) of 0.2 (i.e., alcohol volume fraction of 0.8). Highest Kc values obtained in this study were observed near the equimolar compositions of binary mixtures, behavior similar to the one observed for the extraction of phenol with binary solvent mixtures [6]. On the other hand, in the extraction of antibiotics with primary alcohol/chlorinated hydrocarbon mixtures maximum Kc values in most cases were obtained for the mixtures containing large excess of alcohol [9] and it is worth mentioning that these Kc values were nota bly higher that the ones obtained in this study. Similar Kc values to the ones obtained in this study were reported for the extraction of ascorbic and nicotinic acids with the binary mixtures 1BuOH/aliphatic ester (ethyl or butyl acetate) [10]. RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A
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When comparing the results obtained in this study for the extraction of paracetamol with DEE/1BuOH binary mixtures from 4 mol dm–3 NaCl solution with our previous results for the extraction from 2 mol dm–3 NaCl solution [13] we may note that although D values largely increased with increasing NaCl concentration there was no big difference in the Kc values. It seems that salt concentration has no significant influence on the synergic effect itself, but only largely improves the extraction efficiency. The results obtained in this study may be important for the better fundamental understanding of liquid liquid extraction processes, especially in the case of poorly extractable substances [12]. Also, the use of highly efficient extraction systems may improve the recovery of paracetamol and/or reduce the solvent consumption during the sample preparation step in the analysis of paracetamol in real samples by the var ious analytical methods [2]. CONCLUSIONS Liquid–liquid extraction of paracetamol from aque ous NaCl solutions was performed with diethyl ether, 1propanol, 1butanol, isobutanol, 1pentanol, and binary mixtures diethyl ether/1propanol, diethyl ether/1butanol, and diethyl ether/isobutanol. Among the pure solvents used in this study the best extraction efficacy was obtained for 1butanol. Positive synergic effect was observed in the whole composition range of binary mixtures for all three pairs of solvents investi gated in this study. Maximum values of synergic coef ficients were obtained for nearly equimolar binary mixtures while maximum values of distribution ratios were obtained for the mixtures containing large excess of alcohols. However, it seems that only a combination of Hbond donor component (alcohol) and Hbond acceptor component (diethyl ether) enables optimal extraction of paracetamol. ACKNOWLEDGMENTS This work was supported by the Ministry of Educa tion and Science of the Republic of Serbia under the project no. TR 31060. REFERENCES 1. S. White and S. H. Y. Wong, Clin. Chem. 44, 1110 (1998). 2. M. Espinoza Bosch, A. J. Ruiz Sánchez, F. Sánchez Rojas, and C. Bosch Ojeda, J. Pharm. Biomed. Anal. 42, 291 (2006). 3. L. Hao, C. Zhang, J. Wang, Y. Jiang, J. Paul Fawcett, and J. Gu, J. Pharm. Biomed. Anal. 51, 716 (2010). 4. Ya. I. Korenman and T. N. Ermolaeva, Zh. Prikl. Khim. 65, 2609 (1992). Vol. 87
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13. G. M. Nikoli c´ , J. V. Zivkovi c´ , D. Vlajin, D. Atanask ovi c´ , and M. G. Nikoli c´ , in Proceedings of the 11th International Conference on Fundamental and Applied Aspects of Physical Chemistry, Sept. 21–24, 2012, Bel grade, Serbia (Belgrade, 2012), p. 597. 14. Ya. I. Korenman, N. Ya. Mokshina, and O. A. Pakho mova, Russ. J. Phys. Chem. A 84, 221 (2010). 15. M. Mahramanlioglu and M. Tuncay, Mühend. Bilim. Derg. 7, 415 (2007). 16. A. S. Kertes and C. J. King, Chem. Rev. 87, 687 (1987).
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