Anal. Chem. 1986, 58, 2617-2621
The accuracies obtained and the rapidity of the technique permit the analysis of solid samples on a routine basis. Registry No. Cd, 7440-43-9; Pb, 7439-92-1.
LITERATURE CITED (1) Vollkopf, U.; Grobenski, 2.; Tarnm, R.: Welz, B. Analyst (London) 1985, 110, 573-577. (2) Brady, D. V.; Montalvo, J. G.; Jung, J.; Curran, R. A. A t . Absofpt. News/. 1974, 13, 5-6.
2617
(3) Brady, D. V.; Montalvo, J. G.; Joseph, 0.; Glowacki, G.; Pisciotta, A. Anal. Chim. Acta 1974, 70, 448-452. (4) L'vov, B. B. Spectrochim. Acta, Part8 1978, 3 3 8 , 153-193. (5) Edlger, R. D. At. Absorpt. News/. 1975, 1 4 , 127-130. ( 6 ) Savin, W.; Carnrlck, G. R.: Manning, D. C.; Pruszkowska, E. At. Spectrosc. 1983, 4 , 69-86. (7) Barnett, W. 6.; Bohier, W.; Carnrick, G. R.; Savin, W. Spectrochim. Acta, Part8 1986, 408, 1689-1703.
RECEIVED for review April 21, 1986. Accepted July 1, 1986.
Indirect Determination of Nitrogenated Drugs by Atomic Absorption Spectrometry Cristina Nerh* and Agusth Garnica Departamento de Qulmica, Escuela Tgcnica Superior Ingenieros Industriales, Universidad de Zaragoza, Zaragoza, S p a i n Juan Cacho Departamento de Q d m i c a Analitica, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain
A new procedure for determlnatlon of alkalolds and other pharmaceutical drugs using the Dragendorf reagent is studied. The method consists of extracting an Ion pair between the organic base and the lnorganlc complex BII,- and measuring BI In the organic phase by atomlc absorption spectrometry at 223.1 nm. The opthnal experlmental condltlons pH, concentration of Bl14-, shaking time, phase ratlo, number of extractlons, and the range of calibratlon are studied In the determlnatlon uf dlphenhldramlne, papaverlne, amylocaine, bromhexine, sparteine, and avacan. The organlc phase used Is 1,2dichloroethane. The standard devlatlon of the method Is around depending on the substance analyzed. The new method allows the determlnation of binary mlxtures of alkaloids and drugs. The Interference of forelgn substances that accompany these drugs In pharmaceutlcal preparatlons Is studied. I t Is observed that the Ion pair dlphenhldramineBiI,- Is soluble In 1,Bdlchloroethane.
The indirect determination of organic products by atomic absorption spectrometry (AAS) has long been the subject of research. In 1967, a t the 153rd National Meeting of the American Chemical Society, a paper was read on this subject and was later published (I). Since then, numerous publications have appeared in the literature on AAS and this aspect of indirect determination and have been compiled in the reviews by Kirkbright and Johnson in 1973 (2),Miller in 1978 (3), Roussellet and Thuller in 1979 ( 4 ) ,Kidani in 1981 (5), Ebdon in 1982 Influence of the Concentration of BiI,. Figure 3 shows the influence of the BiI, concentration in the aqueous phase on the extraction of the corresponding ion pair. It is observed that the maximum atomic absorption values are obtained at concentrations above 1.5 X lo4 M Bird- and that, except for papaverine, the atomic absorption values begin to fall slowly above 4.5 X lW3 M BiI,. For papaverine, the maximum value is obtained in the concentration range 8.5 X M to 1.3 X M Bi14-. Above this last value, the extraction yield diminishes, reaching zero a t a concentration of 3.1 X M BiI,-. Shaking Time and Stability. The influence of the shaking time of the phases on the absorbance values was not found to be significant. Shaking times ranging from 15 s to 3 min were studied, with the conclusion that 1 min is enough to obtain constant absorbance values. The stability of the extracts obtained was studied by preparing a stock solution of each extract and comparing its absorbance over a period of time with that of a freshly prepared extract under the same conditions. The extracts of the ion pairs of sparteine, amylocaine, and diphenhydramine are stable for 24 h, that of avacine for 12 h, that of bromhexine for 2 h, and that of papaverine for 20 min. Extraction Yield. The extraction yield of the different ion pairs was determined by comparing the atomic absorption values for bismuth, obtained by directly nebulizing in the flame the extracts in dichloroethane obtained under optimum
100 95.5 98.5 105.1 104.7 103.6 100.8 101.1
Standard devi-
Figure 3. Influence of concentration of Bi1,- in the determination of alkaloids and drugs by AAS: diphenhidremine (O), amylocaine (O), avacan (O),sparteine (A),bromhexine (W), papaverine (A).
conditions, with those of a calibration graph drawn up with solutions of Bi in dichloroethaneobtained by directly weighing out the Bi-diphenhydramine ion pair. It was found that a single extraction gave practically 100% yield for all the ion pairs except that formed by amylocaine (Table I). In this last case, two extractions are required to achieve over 99% recovery.
CALIBRATION GRAPH AND COMPARATIVE STUDY Table I1 gives the optimum conditions for determining the substances, together with those obtained by using Co(SCN)2-
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ANALYTICAL CHEMISTRY, VOL. 58, NO. 13, NOVEMBER 1986
Table 11. Experimental Conditions for Determination of Some Alkaloids and Drugs by AAS Using Different Inorganic Ions BiI, papaverine atropine sparteine avacan quinine pilocarpine amylocaine procaine codeine bromhexine diphenhydramine
2.6 3.5 2.4 2.5 3.2 2.6 Bi1,-
papaverine atropine sparteine avacan quinine pilocarpine amylocaine procaine codeine bromhexine diphenhydramine
1
1 1 1
PH" Co(SCN),22.4 5.4 5.7 6.2 5.4 6.4 3.0 4.5 1.7 2.5
Fe(SCN),3-
BiI,
2.5
0.928
3.6
0.232 0.371
3.0
0.309
3.0
0.185 0.185
2.5 shaking time," min Co(SCN):Fe(SCN),3-
Bi14-
5
0.30 0.45 0.30 0.60 0.45 0.06 0.24 0.45 0.30 1.00
1
1 1
1 1 1
2
1 1 1
1 1
1 1
0.019-0.25 0.006-0.12 0.011-0.23 0.012-0.12 0.012-0.16 0.01-0.10
0-0.63 1.25-3.75 0-0.38 0-0.15 0.2-0.7 0.05-0.3 0-0.24 0.6-2.0 1.0-4.0 0.15-0.6
Bi1,-
0-0.51
0.337 46
0-0.4
0.409 86 0.392 11
0-0.6
0.547 83
0.08-0.7 0-0.7
0.498 81 0.709 58
0.276 0.368 0.368 0.368
1 1 2 2 1 1 1 1 1 1 1
1
1 1
0.276
extraction number" Co(SCN),2Fe(SCN)t-
1
1 1
linear range mg.rnL-l in organic Dhasec Bi14Co(SCN),'Fe(SCN),3papaverine atrophine sparteine avacan quinine pilocarpine amylocaine procaine codeine bromhexine diphenhydramine
concn of inorganic complex* Co(SCN),2Fe(SCN),3-
2 1
2 1 1
slope of calibration graph Co(SCN),2Fe(SCN)B30.091 77 0.016 33 0.090 58 0.128 19 0.076 24 0.121 41 0.175 56 0.028 69 0.007 19 0.061 4
0.055 10 0.091 76 0.061 36 0.0614 0.058 24
'These data represent maximum recovery. For Co(SCN),'- and Fe(SCNI3- concentration are expressed in molarity units. For BiI;, concentration is expressed in M units. cAqueous: organic phase ratio, 51. Table 111. Analysis of Binary Mixtures of Alkaloids and Drugs by AAS
substance papaverine
amylocaine
bromhexine diphenyhydramine
pH
10-3[BiIJ, M
amt added, mg
1.75 1.75 1.75 1.75 2.0 2.0 2.0 2.0 2.0 2.5 2.5 2.5 2.7
0.928 0.928 0.928 0.928 0.185 0.185 0.185 0.185 0.185 0.185 0.185 0.185 0.185 0.185 0.185
1.02 1.02 1.02 1.02 0.977 0.977 0.977 0.977 0.977 1.56 1.56 1.56 0.990 0.990 0.990
2.7
2.7 a Average of three determinations.
and Fe(SCN):as complexing agents. Some interesting conclusions can be drawn from the comparison. Firstly, selectivity is much lower with C O ( S C N ) ~than ~ - with Bi1,- of F ~ ( F J C N )and ~ ~ -that the last two have similar selectivity.
sparteine
atropine
pilocarpine
papaverine
0.988 0.983 0.955 0.988 0.983 0.955 1.02 0.955 1.02 0.955 1.02
recovered" 1.02 1.03 1.01 1.01 0.977 0.978 0.978 0.978 0.979 1.57 1.57 1.56 0.991 0.991 0.992
Therefore, Co(SCN)P i s preferred when we wish to determine the total amount of drug or alkaloid present in a solution, and Bi14- or Fe(SCN)63- will be preferred when we wish to determine one substance in the presence of others, e.g., pa-
ANALYTICAL CHEMISTRY, VOL. 58, NO. 13, NOVEMBER 1986
paverine in the presence of pilocarpine, quinine with atropine, codeine with procaine, etc. Secondly, the pH range that gives the formation and maximum extraction of the ion pairs is very small: approximately 1for BiI; and Fe(SCN)6* and considerably wider for Co(SCN),*-. Therefore, it will be very difficult to carry out differential determination by variation of pH of substances that react with Bi14- or Fe(SCN)63-. The organic complex concentration in aqueous solution that gives the optimum formation and extraction of the ion pair is considerably lower for Bi14- than for Fe(SCN)63- or Co(SCN)42-. Taking into account the similarity with regard to selectivity and p H range between Bi14- and Fe(SCN)63- the advantages of using the BiI, complex are clear. Furthermore, at high concentrations of Fe(SCN):- and CO(SCN),~-polymerization can occur. With regard to extraction yield, the differences tend to favor the use of Bi14-. For example, in determining papaverine, BiI; or Co(SCN)?- are preferred to Fe(SCN)6*; for sparteine, BiI, is preferred; for avacine, better results are obtained with BiI, or Fe(SCN)63-than with Co(SCN)42-;and for amylocaine, C O ( S C N ) ~is~ -preferred. With regard to the interval in which the Beer’s law holds, the widest is obtained by using Fe(SCN)63-,but the slopes of the calibration graphs are considerably higher when BiI,- is used. This means that the sensitivity in the determination using this reagent is much higher, which is in agreement with the fact that it forms ion pairs of stochiometry 1:l with nitrogenated organic substances, and not 2:l or 3:l as is the case with CO(SCN),~-or Fe(SCN)63-, respectively. Interferences. Of the substances studied here which react with Bi14-, atropine, pilocarpine, quinine, and codeine do not interfere with the determination of the other alkaloids or drugs mentioned, because they do not extract into 1,Z-dichlorethane. Procaine interferes with those determinations in which it extracts to a small extent. Foreign substances such as sulfamides, B group vitamins, antibiotics, sugar, excipients, and guayacol glyceryl ether do not interfere in the determination. Analysis of Mixtures. In spite of the small pH interval in which the ion pairs with BiI, are formed and extracted and of the low variation in the optimal concentration interval of this reagent, it is possible to carry out differential determi-
2621
nations of mixtures of substances that react with BiI;, which means that it has high selectivity. So by controlling the pH and the concentration of Bi14-, papaverine has been determined in the presence of sparteine, amylocaine in the presence of papaverine or sparteine, bromhexine in the presene of papaverine or pilocarpine, and diphenhydramine in the presence of pilocarpine or papaverine. The results obtained are shown in Table 111. Registry No. Co(SCN):-, 18904-81-9;Fe(SCN)6*, 45227-67-6; papaverine, 58-74-2;papaverine hydrochloride, 61-25-6;atropine, 51-55-8; atropine sulfate, 55-48-1; sparteine, 90-39-1; sparteine sulfate, 299-39-8; avacan, 54-30-8; avacan dihydrochloride, 5892-41-1;quinine, 130-95-0;quinine hydrochloride, 7549-43-1; pilocarpine, 92-13-7;pilocarpine hydrochloride, 54-71-7;amylocaine, 644-26-8; amylocaine hydrochloride, 532-59-2; procaine, 59-46-1; procaine hydrochloride, 51-05-8; bromhexine, 3572-43-8; bromhexine hydrochloride, 611-75-6; diphenhydramine, 58-73-1; codeine, 76-57-3; Dragendorff s reagent, 39775-75-2.
LITERATURE CITED Christian, G. D.; Feldman, F. J. Anal. Chim. Acta 1068, 40(2), 173. Kirkbright, G. F.; Johnson, H. N. Talanta 1973, 20, 433. Miller, J. H. M. Int. Lab. 1978, 8 , July-August, 37. Rousseiet, F.; Thuller, F. Prog. Atom. Spectroc. 1070, 7 , 353. Kidani, Y. Bunseki Kagaku 1081, 30, 59. Edbon, L. I n Atomic Absorption Spectroscopy; Cantle, J. E., Ed.; EL sevier: Amsterdam, 1982; p 395. Garch Vargas, M.; Milla, M.; P6rez Bustamante, J. Analyst (London) 1983. 108. 1417. Clark; E. R:; Yacoub El-Sayed. A. K. Talanta 1984, 37, 15. The United States Pharmacopeia1 Convention, 1985, X X I . Brltlsh Pharmacopeia/ 1980; H. M. Stationery Office: London, 1980. Gilpin, R. K.; Pachla, L. A. Anal. Chem. 1085, 57, 29R. Meathevall, R. C.; Guay, D. R. P. J . Chromatogr. 1064, 307(2), 295. Gur’ev, I. A.; Chueva, A. K.; Lizuanova, G. M.; Sbitnova, I. A. Farmtslya (Kiev)-l063,32, 80. Cacho, J.; Nerin, C.; Ruberte, L. Anal. Lett. 1983, 76(83),237. Bech, G. E.; Nielsen, A. J . Chromatogr. 1082, 228, 392. Karanya, M. S.; Diab, A. M.; Swecen, N. 2. Anal. Lett. 1984, 17(81), 89.Ne@, C.; Garnica, A.; Cacho, J. Anal. Chem. 1085, 57, 34. Nerin, C.; Cacho, J.; Garnica, A. Anal. Lett. 1985, 78(B15), 1887. Nerin, C.; Garnica, A.; Cacho, J., Zaragoza, Spain, unpublished work,
1988.
RECE~VED for review March 13,1986. Accepted May 23,1986. The authors are grateful to Navarra Government for its assistance in this work (Fora1 Order 707/1985).
