542
Anal. Chem. 1984, 56,542-546
EXPERIMENTAL DESIGN With this calibration, a number of different experimental designs are available but there are strong indications a Calibration involving just two regression lines with one standard addition for each line would be highly efficient. A number of replicate observations should be taken, but it should be remembered that while repeated measurements may be taken after any analyte addition they cannot be performed in random order and are not genuine replications. If T ~represents , the shorter accumulation time it should be small and compatible with the requirements for stabilizing Ibg;the analyte addition AC, should be as large as possible but consistent with on scale I,,. If T~ represents the longer accumulation time it can be shown that the anal* addition ACZ should be slightly larger than C, and T~ should be as large as possible but again compatible with on scale I,,. With such a design more than half the observations should be made at and for each line about twice as many observations should be made on the unspiked sample as on the sample after analyte addition. Table I1 summarizes data from five experiments involving the determination of trace amounts of As(II1) added to a “clean” seawater sample. The arsenic present in the sample itself was present in the electroinactive As(V) form. C, was determined as the intersection of the two least-squares Calibration lines, while the 95% confidence interval was deter-
mined by each of the three outlined methods. Good agreement among added and found As(II1) and among the confidence intervals can be observed. The calibration method has obvious applications in those cases where Ibg is an unknown, provided that it remains constant through the whole set of analyses. Registry No. As, 7440-38-2; water, 7732-18-5.
LITERATURE CITED (1) Corsini, A.; Wan, C. C.; Chiang, S. Talanta 1982, 29, 857-860. (2) Copeiand, T. R.; Christie, J. H.;Osteryoung, R. A.; Skogerboe, R. K. 4nal. Chem. 1973, 4 5 , 2171-2174. (3) Kernula, W. Pure Appl. Chem. lg67, 15, 283-298. (4) Wang, J.; Greene, B. Anal. Chlm. Acta 1982, 744, 137-145. (5) Whang, C.-W. Ph.D. Thesis, Queen’s University, Kingston, Ontario, Oct 1983. (6) Kendall, M. G.; Stuart, A. “The Advanced Theory of Statistics”, 3rd ed.; Hafner Publishing Co.: New York, 1973; Vol. 2. (7) Draper, N. R.; Smith, H. “Applied Regresslon Analysis”, 2nd ed.; Wiiey: New York, 1980. (8) Box, 0. E.; Tiao, G. C. “Bayesian Inference in Statistical Analysis”; Addison-Wesley Publlshlng Co.: New York, 1973.
RECEIVED for review August 26, 1983. Accepted December 5, 1983. We are grateful to the Marine Analytical Program of the National Research Council of Canada for contract support and the National Sciences and Engineering Research Council of Canada for support in the form of operating and strategic grants.
Liquid and Poly(viny1 chloride) Atropine-Reineckate Membrane Electrodes for Determination of Atropine Saad S. M. Haasan* and F. Sh. Tadros Department of Chemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
Llquld and poly( vlnyl chlorlde) membrane electrodes, which are sensitive and reasonably selecllve for atroplne, are developed. They are based on the use of an atropine-relneckate Ion palr complex as a novel electroactlve materlal in elther benzyl alcohol or poly(vlnyl chlorlde) matrlx. Both electrodes exhlblt rapld response In the range of loe2to 5 X lo-’ M atroplne over a pH range of 3.5-8.5 with a catlonlc slope of 57 mV/concentratlon decade. As llttle as 1 Hg/mL of atroplne can directly be measured with an average recovery of 98.7% (standard devlatlon 1.8%) and wlthout Interference from many organlc and lnorganlc cations as well as exclplents commonly used In drug formulatlon. Determlnation of atroplne In some pharmaceutlcal preparations by both electrodes glves results which compare favorably wlth those obtalned by the Unlted States and Brltlsh Pharmacopoeia methods.
Atropine is one of the tropane alkaloids used to stimulate the medulla and higher cerebral centers. It blocks the responses of the sphincter muscle of the iris and the ciliary muscle of the lens to cholinergic stimulation. It is also used to counteract the periferal vasodilatation and sharp fall in blood pressure caused by choline esters. Existing methods for the determination of atropine are based on either direct thermometric ( I ) , turbidimetric (2),conductometric (3) and potentiometric (4) titrations with acids and heteropoly acids, or reaction with lead or copper picrate (5,s) followed by visual complexometric titration of the excess metal with EDTA. 0003-2700/84/0358-0542$01.50/0
Both the United States and British Pharmacopoeias recommend extraction of atropine base and dissolution in acids followed by visual titration with alkali (7,8).None of these methods, however, can be applied for the determination of atropine in concentrations less than 1 mg/mL or in the presence of other basic substances. Spectrophotometry (9, lo), fluorimetry (11), gas-liquid chromatography (121, high-performance liquid chromatography (13), and radioimmunoassay (14) afford more sensitive and selective methods for quantitation of low levels of atropine, but they all involve several manipulation steps and require expensive reagents and sophisticated instruments. Membrane electrodes for some alkaloids have recently been developed and shown to be simple and sensitive monitoring sensors (15). These electrodes are based on dispersing tetraphenylboron or dipicrylamine complexes of the alkaloid, as electroactive material, in polymeric or liquid membranes. On this basis, electrodes sensitive for atropine (16),novocaine (15, 17), nicotine (18), codeine (15, 19, 20), morphine, ethylmorphine (20), neostigmine, methacholine, ephedrine, and methylephedrine (20) have been described. In view of the fact that tetraphenylboron and dipicrylamine react not only with various alkaloids but also with tertiary amines, quaternary ammonium salts, arendiazonium salts, and some metals, these electrodes are poorly selective. Dinonylnaphthalenesulfonic acid (21,22)and picrolonic acid (23) have proved to be suitable alternative reagents for the preparation of membrane electrodes reasonably selective for some alkaloids. On the other hand, atropine and some other alkaloids form water-insoluble precipitates with ammonium reineckate. 0 1984 American Chemical Society
ANALYTICAL CHEMISTRY, VOL. 56, NO. 3, MARCH 1984
Isolation of the precipitate and its dissolution in organic solvents permit determination of their alkaloid derivatives either by measuring the absorbance of the color at 530 nm (24), by titration with mercury(I1) using diphenylcarbazone indicator (25),or by atomic absorption spectrometric measurement of chromium (26). The present work, however, describes sensitive and reasonably selective liquid and poly(vinyl chloride) membrane electrodes based on the use of atropine-reineckate as a novel electroactive material. These electrodes are satisfactorily used for the determination of as little as 1 pg/mL of atropine with good precision and with minimal interference from basic substances. EXPERIMENTAL SECTION Apparatus. Potentiometric measurements were made with an Orion Microproceasor Ionanalyzer (Model 901) using the liquid and PVC atropinereineckate membrane electrodes in conjunction with an Orion double junction silver/silver chloride reference electrode (Model 90-02) with 10% potassium nitrate in the outer compartment. All measurements were conducted at a constant temperature in the range of 25-30 OC. The pH adjustment was conducted with an Orion combined glassdome1 electrode (Model 91-02). The infrared spectra were measured with a Unicam 200 G spectrometer and the mass spectrum was taken with a Varian CH-7 mass spectrometer. Reagents. All the reagents used were of analytical reagent grade. Double distilled water and solvents were used throughout. Atropine, atropine salts,and ammonium reineckate were obtained from Sigtna Chemical Co. (St. Louis, MO). Chromatographic grade poly(viny1 chloride) was obtained from Polyscience, Inc. (Washington, PA). Pharmaceutical preparations containing atropine were obtained from local drug stores. Atropine-Reineckate Ion Pair. A 20-mL aliquot of 0.1 M atropine hydrochloride and 30-mL aliquot of 0.1 M ammonium reineckate solutions were mixed and stirred for 15 min. The pink precipitate was filtered with a G3 sintered glass crucible,washed with double distilled water, followed by ethanol, dried at 100 OC for 1 h and ground to fine power. Liquid Atropine-Reineckate Membrane Electrode. An Orion liquid membrane electrode barrel (Model 92) was used as the electrode assembly with an Orion 92-81-04 porous membrane (- 100 pm pore diameter) to separate the organic phase from the test solution. The organic phase was 0.01 M atropine-reineckate in benzyl alcohol and the aqxous reference solution was a mixture of equal volumes of 0.02 M atropine hydrochloride and 0.1 M potassium chloride. PVC Atropine-Reineckate Membrane Electrode. Atropine-reineckate ion pair (-0.03 g) was dissolved in 5 mL of benzyl alcohol and added to a solution of 0.3 g of PVC in 5 mL of cyclohexanone and 1mL of dioctyl phthalate. The mixture was stirred thoroughly until complete dissolution. The solution was then poured onto glass casting ring with an internal diameter of 35 mm with one end ground to give flush contact with the glass plate. After 2 days, a master membrane 0.3 mm thick was obtained. A 3 cm long PVC tube (6 mm external diameter) was dipped from one end into tetrahydrofuran solvent and the tube was held in a vertical position while rubbing the dipped end on a glass plate in a circular and rotatory fashion. A disk of the master membrane corresponding to the external diameter of the PVC tubing was carefully cut out and mounted, with a forceps, on the polished end of the PVC tubing. The outer edge of the circular membrane was sealed to the end of the PVC tubing with a PVC solution in tetrahydrofuran as adhesive (the adhesive should not come into contact with the sensing surface of the membrane). The other end of the PVC tubing was connected to a suitable glass tube and the tube waa filled with equal volumes of 0.02 M atropine hydrochloride and 0.1 M potassium chloride solution. A silver-silver chloride electrode wire (0.5 mm diameter) was inserted into the solution and connected to a cable. Electrode Calibration. Both liquid and PVC atropine-reineckate membrane electrodes were preconditioned by soaking in a solution of 0.1 M atropine hydrochloride for 2 days after preparation. The electrode was then stored in deionized water. Twenty-milliliter aliquots of 10-z-10-6 M atropine hydrochloride solutions in 0.1 M potassium nitrate background were then placed
543
into 100-mL beakers, and the pH was adjusted to 4-6 by addition of dilute sulfuric acid and/or sodium hydroxide solutions. The liquid or PVC atropine-reineckate membrane electrode was immersed in conjunction with a double junction reference electrode (Orion 90-02) into the solution. The solutions were stirred and the potential readings were recorded when becoming stable and were then plotted as a function of the logarithm of atropine concentration. The graph was used for subsequent measurement of atropine containing samples. Determination of Atropine in Pharmaceutical Preparations. The contents of five ampules of 1% atropine injections (1mL each) or 5-mL aliquots of 0.5-1% atropine eye drops were transferred to a 100-mL measuring flask, diluted to the mark with deionized water, and shaken. Then 2-8-mL aliquots of the solutions were transferred to a 100-mL beaker and diluted to 20 mL with 0.1 M potassium nitrate and the pH was adjusted to 4-6. Either liquid or PVC atropine-reineckate membrane electrode was immersed in the solution in conjunction with a double junction reference electrode. The potential readings were recorded when becoming stable and compared with a calibration graph prepared from pure standard atropine solutions. Atropine in 1% atropine eye ointment was determined after a prior extraction using the United State Pharmacopoeia method (7). An accurately weighed 10 g of the ointment was dissolved in 20 mL of diethyl ether and treated, in a 100-mL separating funnel, with five successive 10-mL portions of 0.1 N sulfuric acid. The aqueous extract was collected, made alkaline with 20% aqueous ammonia, and extracted with five successive 15-mL portions of chloroform. The chloroform extract was evaporated to dryness and the residue dissolved in 100 mL of 0.05 N sulfuric acid. The atropine content of 2-8-mL aliquots of the solution was measured as described above. RESULTS AND DISCUSSION Membrane Material. Atropine reacts with ammonium reineckate to form a stable water-insoluble 1:1type of complex whose composition (structure I) was verified from elemental 0 C,H,-
C H - E - O a t l [Cr(NH,l,
(SCN),]'
2H,O
CH,OH
(I 1 analysis data, molecular weight determination, and infrared spectrometry. The signals obtained at m / z values corresponding to M+, (M - l)+, and (M + 1)+in the mass spectrum of the complex and the elemental analysis data agree with the molecular formula C21H30N7S403Cr-2H20.The infrared spectra of both the reactants and the complex show that the stretching vibration band at 1400 cm-' which is due to NH,+ in the reagent disappears in the spectrum of the reaction product. The stretching vibration a t 2100 cm-l due to SCN group in the reineckate ion of the reagent and all the fundamental stretching vibration bands of the functional groups in atropine (Le., V C ~ V , ~ H VC-H) , appear a t almost the same position in the spectrum of the complex. The solubility of atropine-reineckate in various water-immiscible organic solvents was tested. The complex exhibits very low solubility in tetrahydrofuran, n-hexane, cyclohexane, benzene, chlorobenzene, dichlorobenzene, chloroform, and carbon tetrachloride but is readily soluble in nitrobenzene, nitrotoluene, n-octanol, and benzyl alcohol. The solubility increases in the order: benzyl alcohol > n-octanol > nitrotoluene > nitrobenzene. The response characteristics of liquid membrane electrodes prepared from 0.1 M solutions of atropine-reineckate in the last four solvents were evaluated. Least-squares analysis of these data is given in Table I. These results show that benzyl alcohol gives a fairly stable and sensitive membrane as indicated by the high slopes, correlation coefficient, low limit of detection, and small standard deviation. With 5 X to M atropine-reineckate solution in benzyl alcohol as liquid membrane, the electrode displays
544
ANALYTICAL CHEMISTRY, VOL. 56, NO. 3, MARCH 1984
Table I. Response Characteristics of Liquid and PVC Atropine-Reineckate Membrane Electrodes a
a
parameter
nitrobenzene
nitrotoluene
slope, mV/log C std dev, mV coir t oeff intercept, mV lower limit of linear range, M detection limit, M
53.5 0.6 0.9970 256.1 6X 3 x 10-5
49.1 0.8 0.9930 242.2 8 x 10-5 2 x 10-5
n-octyl alcohol benzyl alcohol 49.4 0.7 0.9996 229.4 5 x 10-5 3 x 10-5
PVC
56.6 0.6 0.9998 254.8 5 x 10-6
57.0 0.5 0.9998 195.9 5 x 1010-6
10-6
Measurements made with a 0.1 M KNO, background at 25 "C. Table 11. Selectivity Coefficient for Atropine-Reineckate in Benzyl Alcohol and PVC Matricesa Kaj
AgIAgC1 0.01 M atropine0.1 M KC1 reineckate in 0.1 M atropine benzyl alcohol hydrochloride or PVC
test reference solution electrode
I
substance
benzyl alcohol
aminobenzoic acid aminopropanol ethanolamine diethylamine dibutylamine triethanolamine tetramethylammonium chloride piperidine ammonium chloride glycine cysteine urea succinamide strychnine caffeine nicotine
1.1x 1 0 - 2 4.1 X 10.' 3.5 X l o - ' 1.4 X lo-' 5.6 X lo-' 5.7 x 10-1 5.8 X l o - '
1.6 5.2 1.7 2.3 7.5 2.0 3.0
1.3 X 1.3 x 1.4 X 1.3 X 2.5 X 1.4 x 2.83 2.02 1.82
2.1 X lo-' 3.5 x 10-3 4.1 X 4.7 X lo-' 1.1X lo-' 1.2 x 10-3 2.35 1.98 1.66
10" 10-3 10.'
lo-'
lo-'
10-3
PVC
x 10-3
lo-, lo-'
X X X lo-' X lo-'
x 10-l X
10.'
a Measurements made with a 0.1 M KNO, background at 25 "C.
2oo 160
t
P
E
u
(3)
m ._ Y
where S is the slope of the calibration curve of atropine, n is the charge of the foreign substance, AE is the change in potential in the presence of the interfering substance j, and aatropine and uj are the concentrations of atropine and the interfering substances, respectively. The results obtained (Table 11) show that both liquid and PVC atropine-reineckate membrane electrodes exhibit negligible interference from many basic substances added to atropine at concentrations of 100- to 1000-fold excess. Triethanolamine and tetramethylammonium chloride if present at concentrations >lO-fold excess of atropine interfere. The electrodes respond, however, to nicotine, caffeine, and strychnine. A detailed study of the response characteristics of these electrodes as well as other alkaloid-reineckate membranes is currently under way. Effect of pH. Potential measurements by both liquid and PVC atropine-reineckate membrane electrodes were made on atropine solutions of different pH values. No significant change of the electrode potential was observed over the pH range 3.5-8.5 (Figure 1). The potential difference did not exceed 4 mV within the entire range of pH over the concentration range of to M of atropine. At higher pH values, however, there is a substantial decrease in the potential
C a,
a
-8 0
I
Flgure 1. Effect of pH on potentials of (0)liquid and (0)PVC atropine-reineckate membrane electrodes at various atropine concentrations.
because of the gradual increase in the concentration of unprotonated atropine and precipitation of atropine base. Response Time. The responses of both liquid and PVC atropine-reineckate membrane electrodes were determined
ANALYTICAL CHEMISTRY, VOL. 56, NO. 3, MARCH 1984
545
Table 111. Determination of Atropine by Using Liquid and PVC Atropine-Reineckate Membrane Electrodes a liquid membrane PVC membrane wt added, wt found,b recovery, % wt found,b recovery, % sample ,ug/mL &mL % std dev ,ug/mL % std dev atropine sulfate
atropine base
a
175.0 90.0 35.0 25.0 15.0 10.0
173.0 88.8 34.7 24.5 14.7 9.8
98.9 98.7 99.1 98.0 98.0 98.0
1.7 1.9 1.4 1.5 1.6 1.8
174.0 89.0 35.0 24.8 14.8 9.8
99.4 98.9 100.0 99.2 98.7 98.0
1.3 1.7 1.7 1.5 1.5 2.0
15.0 10.0 7.0 5.0 3.0 1.0
14.6 9.8 6.9 4.9 3.0 1.0
97.3 98.0 98.6 98.0 100.0 100.0
2.1 1.7 1.8 1.9 1.6 2.2
14.7 9.8 6.8 5.1 2.9 1.0
98.0 98.0 97.1 102.0 96.7
1.7 1.6 1.7 2.1 1.4 2.0
Measurements made with a 0.1 M KNO, background at 25 "C.
100.0
Average of three measurements.
Table IV. Determination of Atropine in Some Pharmaceutical Preparations by Using Liquid and PVC Atropine-Reineckate Membrane Electrodesa
preparation atropine sulfate, injectionC isopto atropine, eye dropd isopto atropine, eye dropd atropine eye ointmentC
nominal amt as atropine 1mg/mL
10 mg/mL 5 mg/mL 1 0 mg/g
USP method ( 7 ) liquid membrane PVC membrane recovery,b % recovery,b % recovery,b % % std dev % std dev % std dev 98.2 98.6 97.8 97.7
2.4 2.1 2.0 2.2
98.8 99.0 98.3 98.6
1.5 1.6 1.8 1.8
Average of three measurements. a Measurements made with a 0.1 M KNO, background at 25 "C. El-Nile Pharmaceutical Co., Egypt. Obtained from Alcon Pharmaceutical Co., Belgium. by measuring the time required for the electrodes to attain a steady potential (*0.2 mV) after successive immersion in different atropine solutions each having a 10-fold difference in concentration. The time required to achieve a steady potential by rapid 10-fold increase of atropine concentration to the same solution was also measured. Both results indicate an average response time of 0.5,1,3, and 4 min. for lom2, IO4, and 10" M atropine solutions, respectively. The PVC membrane electrode shows, in general, superior time response behavior to the liquid membrane electrode. The presence of 10-fold excess of many foreign substances (see Table 11) has no influence on the response time and initial calibration curve slopes of both electrodes. The life span of the electrodes is 4 weeks. Determination of Atropine. Table 111presenb the results obtained for direct potentiometric determination of pure atropine solutions using the calibration method. The average recovery of 12 samples each in triplicate and containing 1-200 I g l m L using both liquid and PVC atropine-reineckate electrodes is 98.7% and the standard deviation is 1.8%. The repetability is better than 2%. The effect of a number of pharmaceutical additives and diluenta commonly used in drug formulation (e.g, acacia, Tween-80, ethylene glycol, carboxymethylcellulose, cocoa butter, and paraffin oil) was also examined. No significant effect was noticed due to the presence of 100-fold excess of any of these additives. Determination of atropine in some pharmaceutical preparations was next tried after a simple extraction or dilution step. The results obtained for some injections, eye drops and eye ointments containing 0.1 to 1% of atropine, are summarized in Table IV. The average recovery of the nominal values is 98.8% and the standard deviation is 1.7%. These results are in good agreement with those obtained by both the USP and BP methods (average recovery 98.1 %, standard deviation 2.2%) which involve prior extraction of atropine base, dissolution in standard sulfuric acid, and back titration with sodium hydroxide using methyl red indicator (7,8).These
99.1 99.4 98.7 98.5
1.6 1.5 1.8 1.7
Obtained from
official methods cannot be applied in the presence of other basic substances. The present procedure, however, involves less manipulation steps and offers the advantages of higher selectivity, greater precision, and applicability to atropine samples containing as little as 1 pg/mL in the presence of other basic compounds. Registry No. Atropine, 51-55-8; poly(viny1chloride) (homopolymer), 9002-86-2; reineckate, 16248-93-4; benzyl alcohol, 100-51-6. LITERATURE CITED (1) Bark, L. S.; Grlme, J. K. Anal. Chim. Acta 1973, 6 4 , 276-279. (2) Slchko, A. I. Khim.-farm. Zh. 1978, 72, 140-142. Chem. Abstr. 1979, 9 1 , 13199a. ( 3 ) Plasecka, H. Farm. Pol. 1975, 37, 123-127. Chem. Abstr. 1975, 83, 1033152. (4) Posgay, E. Acta Pharm. Hung. 1965, 35, 68-74. Chem. Abstr. 1965, 63, 1655e. (5) Gajewska, M. Chem. Anal. (Warsaw) 1973, 78, 313-317. Chem. Abstr. 1973, 7 9 , 970166. (6) Rolskl, S.; Gajewska; M.; Matusak, E. farm. Pol. 1969, 2 5 , 111-117. Chem. Abstr. 1969, 7 0 , 109183h. (7) "The United States Pharmacopoela XX Rev"; Mack Publishing Co.: Easton, PA, 1980; pp 39-40. (8) "British Pharmacopoeia Vol. I"; The University Press: Cambridge, 1980; pp 40-41. (9) Nir-Grosfeld, I.; Welssenberg, E. Drug Stand. 1957, 25, 180-185. (IO) Akopyan, 0. A. Apfechn. Delo 1958, 7 , 19-22. Chem. Abstr. 1958, 56, 6307e. ( 1 1 ) Laugel, P. C . R . Hebd. Seances Acad. Sci. 1962, 255, 692-694. Chem. Abstr. 1982, 5 7 , 1 5 2 4 0 ~ . (12) Nlemlnen, E. Zenfralbl. Pharm Pharmakother Laboratoriums dlagn. 1971, 770, 1137-1144. Chem. Abstr. 1972. 7 6 , 1 0 3 8 0 4 ~ . (13) Walters, M. J. J. Assoc. Off. Anal. Chem. 1978, 61. 1428-1432. (14) Vlrtanen, R.; Kanto, J.; Ilsalo, E. Acta Pharmacoi. Toxicol. 1980, 4 7 , 208-212. (15) Ma, T. S.; Hassan S. S. M. "Organic Analysis Using Ion Selectlve Electrodes": Academic Press: London, 1982; Vol. 2, pp 150-164. (16) Dlamandls, E. P.; Athanaslou-Malakl, E.; Papastathopoulos, D. S.; HadjllOannOU, T. P. Anal. Chlm. Acta 1981, 128, 239-244. (17) Negolu, D.; Cosofret, V. V. Talanfa 1981, 2 8 , 377-381. (18) Efstathiou. C. E.; Dlamandls, E. P.; Hadjlioannou, T. P. Anal. Chlm. Acta 1981, 127, 173-180. (19) Hoplrtean, E.; Kormos, F. Chem. Anal. (Warsaw) 1980, 2 5 , 209-213. Chem. Abstr. 1980. 93, 2455391. (20) Ooina. T.; Hobai, S.; Rozenberg, L. farmacia (Bucharest) 1978, 26, 141-147. Chem. Abstr. 1979, 90, 76618m. I
.
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Anal. Chem. 1084, 56,546-549
Martin, C. R.; Frelser, H. Anal. Chem. 1980,5 2 , 1772-1774. Cunningham, L.; Freiser, H. Anal. Chlm. Acta 1982, 139, 97-103. Hassan, S. S. M.; Eisayes, M. B. Anal. Chem. 197P,5 1 , 1651-1654. Weyer, J.; Sk&a, M. Dlss. Pharm. 1082, 14, 201-205. Chem. Abstr. 1962,5 7 , 167461. (25) Peiczar, T. Acta Pol. Pharm. 1072,2 9 , 465-468. Chem. Abstr. 1972,78,8 5 6 4 0 ~ .
(21) (22) (23) (24)
(26) Minamikawa, T.; Matsummura, K. Yakugaku Zasshi 1978, 96, 440-446. Chem. Abstr. 1978,8 5 , 25436s. (27) Srinivasan, K.;RechnRz, G. A. Anal. Chem. 1989, 4 1 , 1203-1205.
for review August l9, 1983. Accepted November 14, 1983.
Mass Spectral Characterization of Oxygen-Containing Aromatics with Methanol Chemical Ionization Michelle V. Buchanan Analytical Chemistry Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831
Chemlcai ionlzation mass spectrometry with methanol and deuterated methanol as lonlzatlon reagents Is used to differentlate oxygen-contalnlng aromatks, Including phenols, aromatic ethers, and aromatic substltuted alcohols, as well as compounds contalnlng more than one oxygen atom. The analogous sulfur-containing aromatics may be slmilarly dlfferentiated. Methanol chemlcal lonlzatlon Is used to characterize a neutral aromatic polar subfraction of a coal-derlved liquid by combined gas chromatography/mass spectrometry.
Conventional electron impact ionization mass spectrometry is rather limited in its ability to distinguish isomeric compounds. This is particularly true for isomeric oxygen-containing aromatics such as hydroxy aromatics (phenols), aromatic ethers, and aromatic substituted alcohols. For example, the electron impact mass spectra of 2,6-dimethylphenol (I) and 1-methoxy-2-methylbenzene(II), both with molecular weights of 122, are very similar and thus difficult to distinguish. Chemical treatment with trifluoroacetic anhydride or other reagents is often used to derivatize compounds with active hydrogens (1,2), such as phenols (I) and aromatic alcohols (111). The mass spectra of these compounds then distinguish them from compounds with no active hydrogens, such as aromatic ethers (11). However, both phenols and aromatic substituted alcohols undergo derivatization and their mass spectra cannot be differentiated.
Chemical ionization (CI) using deuterated reagents has been successfully used to assess the number of active hydrogens on heteroatoms (3-5). This same type of approach has also been used to differentiate isomers of simple amines (6) and, more recently, nitrogen-containing aromatics (7),using ammonia and perdeuterioammonia as CI reagents. In the present study, a similar approach using methanol and its deuterated analogue (either CD30D or CH30D) as CI reagents has been used to differentiate isomeric oxygen-containing aromatics, including hydroxy aromatics (phenols), aromatic ethers, and aromatic substituted alcohols. A polar subfraction of a coal-derived liquid composed primarily of oxygen-substituted aromatics has also been characterized by using methanol chemical ionization mass spectrometry. 0003-2700/S4/0356-0546$01.50/0
Table I. CH,OH/CD,OD CI Mass Spectra of Oxygen-Containing Aromaticsa
mlz m Iz mol CH,OH CD,OD compound wt CI CI Phenols p-methylphenol 108 109 111 125 3,4-dimethylphenol 122 123 2,4,6-trimethylphenol 136 139 137 2-isopropylphenol 136 139 137 2-sec-butylphenol 150 153 151 4-indanol 134 137 135 5-indanol 134 137 135 7-methyl-5-indanol 148 151 149 2-naphthol 144 147 145 161 2-methyl-1-naphthol 158 159 171 173 o-phenylphenol 170 2-hydroxydiphenylmethane 184 187 185 Ethers anisole 108 109 110 allyl phenyl ether 134 135 136 171 phenyl ether 170 172 185 186 benzyl phenyl ether 184 159 160 1-methoxynaphthalene 158 159 2-methox ynaphthalene 158 160 2-ethoxy naph thalene 172 173 174 Alcohols 105 p-methylbenzyl alcohol (b) 122 105 117 117 3-phenyl-2-propenol(l0) 134 117 1-indanol(2") 134 117 141 141 158 1-naphthalenemethanol ( b ) 155 1-naphthalenethanol(1") 172 155 243 243 triphenylmethanol(3") 260 Compounds Containing More Than One Oxygen 1,2-dimethoxybenzene 138 139 140 guiacol (o-methoxyphenol) 124 125 127 1-methoxybenzyl alcohol 138 121 121 3-methylcatechol 124 125 128 2,3-dimethoxyphenol 154 155 157 a Only base peak shown, peaks from cluster species and natural isotopic species not shown. Type of substitution of the alcohol is noted in parentheses as follows: b, benzylic; lo,primary; 2", secondary, 3", tertiary.
EXPERIMENTAL SECTION Mass spectra were generated with a Hewlett-Packard 5985 gas chromatograph/mass spectrometer (GC/MS) equipped with a dual electron impact/chemical ionization source. The CI reagents, 0 lg64 American Chemlcal Soclety
