摘要:

ANALYST, MAY 1992, VOL. 117 92 1 Determination of Mercury(i1) by Its Inhibitory Effect on the Enzymic Reaction of Ethanol Oxidation Using Flow Injection M. Jesus Almendral Parra, Angel Alonso Mateos, Candido Garcia de Maria and Leonor G. Rozas Departamento de Quimica Analitica, Nutricion y Bromatologia. Facultad de Quimica, Universidad de Salama nca, 37008, Sa la manca, Spain A flow injection procedure is described for the determination of Hg*+, based on its non-competitive inhibition of the catalytic effect of alcohol dehydrogenase on the oxidation of ethanol by the coenzyme nicotinamide adenine dinucleotide. Mercury can be determined within the range 0.5-20 ppm with a relative standard deviation of I-1.5% and at a sampling rate of 120-150 h-1. Only Ag+ was observed t o interfere.Keywords: Mercury(//); enzymic determination; flow injection; inhibition reaction Among kinetic analytical methods, in the past few decades enzymic reactions have acquired considerable importance in analytical chemistry; this is essentially because of the great selectivity (sometimes specificity) of enzymes as catalysts for a given reaction. In some instances, enzymic activity increases or decreases owing to the presence of substances, mainly inorganic ions, that bind to the enzyme or to the substrate. This effect, both inhibitory and activating, has been exploited in analytical chemistry as a sensitive and selective method for the determi- nation of numerous species; work in this field is of interest, both from the clinical and toxicological viewpoints.1-5 Also of importance is the potential of this type of determination in view of its application to the determination of metal ions at trace levels. Apart from the work of Baum and Czok6 on the determination of Mg, that of Townshend and co-workers'-12 is also of interest; these workers offered the first reports on the inhibition of the enzyme alcohol dehy- drogenase by heavy metals. NAD+ + C2HSOH C NADH + CH3CHO + H+ (1) The optimum catalysis for the oxidation of ethanol occurs at pH 8.7, and at pH 5.5-6.5 for the reverse reaction. The determination of ethanol and acetaldehyde in different types of sample, with use of this reaction as a basis, has been the subject of several studies involving flow injection (FI). 13-15 The present paper reports on the results obtained in the study of the inhibitory effect of Hg2+ on this reaction [eqn.(l)] by use of the FI technique, with a view to developing a procedure for the determination of Hg, which can be used in routine analysis. The technique was found to offer noteworthy advantages, with respect to selectivity, incubation times and sampling rate, over other procedures described for this type of determination .7-9 Experimental Apparatus A Gilson 2HP4 Minipuls peristaltic pump (Worthington, OH, USA), a rotatory injection valve of poly(tetrafluoroethy1ene) (PTFE) (Tecator L-100-1; Herndon, VA, USA) with six ports (three for inflow and three for outflow), and PTFE tubing of 0.5 and 0.7 mm i.d. with normalized Rheodyne tube endings (Cotati, CA, USA), were used. Linear and T-shaped connec- tors were made of Perspex, the T connectors being constructed with internal diameters of 0.7 and 1.0 mm.A Unicam 1800 UVhisible Spectrophotometer, equipped with a Unicam AR-25 linear recorder and a flow cell of 38 p1 and 10 mm optical pathlength in Suprasil I quartz glass (Hellma, Jamaica, NY, USA), was also used. Reagents Lyophilized alcohol dehydrogenase (E. C. 1.1.1.1). Solutions were prepared by diluting suitable amounts of the enzyme (Boehnnger, Mannheim, Germany) in pyrophosphate buffer solution (pH range 7-9) containing gelatin (10 mg dl-1) and ammonium sulfate (0.4 g dl-1) as stabilizers. Nicotinamide adenine dinucleotide ( N A D+ ) oxidoreductase. This enzyme (Boehringer), at a purity of 100% was prepared in pyrophosphate buffer solution in the pH range 7.8-9.Pyrophosphate buffer solution. Prepared from 33.4545 g of sodium pyrophosphate, 8.3647 g of semicarbazide hydro- chloride, 1 S768 g of glycine, 8.7660 g of sodium chloride and 1 mol dm-3 sodium hydroxide (as necessary to adjust the pH to the working conditions), all in 1 1 of solution. Ethanol. Solutions, at various concentrations between 55 and 2000 ppm, were prepared from the chromatographic reagent. Standard solutions (at 100 ppm) of Hg2+, Ag+ , Cu2+, Pb2+ and Zn2+ were prepared from analytical-reagent grade chemicals by dissolution in distilled water with a few drops of HN03. More dilute solutions were prepared immediately before use by appropriate dilution of the standard solutions. Adsorption of metal ions onto glass walls Both mercury and silver are adsorbed by glass, which could lead to errors in the determination of low concentrations of these elements.These errors can be minimized by leaving the solution in contact with the glass for as short a time as possible or by inducing saturation by maintaining a solution of equal concentration in the vessel over a certain period of time (12 h). Procedure In the FI scheme depicted in Fig. 1, distilled water is introduced into the carrier channel C1, while a solution of ethanol (500 or 1000 ppm) in pyrophosphate buffer, pH 8.7, is introduced through the confluence channel C2. The resulting solution is made to merge at a second merging point with a third solution, circulating through carrier channel C3 formed from a mixture of enzyme (20 mg dl-1 or 40 mg dl-1) and coenzyme (48 mg dl- * or 80 mg dl- I ) , keeping the flow rate for all solutions constant at 1 ml min-1. Mercury solutions are injected (126 pl) into channel C1.After mixing and reaction in reactor R2 (1.25 m), the signal corresponding to the absor- bance at 340 nm is recorded. Both reactors R1 and R2 should be thermostatically controlled in glass tubes containing water at 25 "C. The reagents circulating through C1, C2 and C3 are thermostatically controlled in a water-bath at the same temperature.922 I Ethanol in pyrophosphate buffer c2 Enzyme and 1 .o ANALYST, MAY 1992, VOL. 117 coenzyme c3 0.4 1 1 .o I 1 0 B 1 Tl 4 H 14 min 1 Time - Fig. 1 FI system of optimum confluence for the determination of mercury by continuous flow (IV = injection valve and FC = flow cell) and analytical signal obtained for different concentrations of mercury ( P P d Results and Discussion Design of the Flow System The proposed flow system is shown in Fig.1. Solutions of Hg" are introduced directly into the carrier channel containing distilled water and are made to merge with the solution of ethanol in pyrophosphate buffer in reactor R1 and then with the solution of enzyme, coenzyme and pyrophosphate in reactor R2. In the absence of Hg", the confluence of the three channels gives rise to a constant signal for reduced nicotinamide adenine dinucleotide (NADH), which is measured at 340 nm, induced by the oxidative enzymic conversion of ethanol into acetaldehyde in the presence of alcohol dehydrogenase. In the presence of Hg", the inhibitory effect of this species on the reaction brings about a decrease in the constant signal obtained, which is modified when the concentration of Hg" injected decreases (Fig.1). Study of Variables The effect of the following experimental variables on the efficiency of the inhibition was investigated within the indicated ranges: pH (7-9), concentrations of coenzyme (16.0-80.0 mg dl-I), enzyme (4.0-40.0 mg dl-*), ethanol (55-1000 ppm) and Hg (1-15 mg I-'), length of reactor R2 (0.5-3.0 m), injection volume (50-500 PI) and flow rates (0.5-2.0 ml min-1). The reaction will occur with greater sensitivity under the optimum conditions of the enzymic reaction, i.e., at pH 8.7. This pH was accordingly chosen as the optimum value for later studies. At a given concentration of Hg" (approximately 7 ppm) and as the concentration of coenzyme rises, an increase occurs in the analytical signal (AA).This indicates that the inhibitory effect increases in absolute values as the rate of the non- inhibited reaction increases. Additionally, for Hg concentra- tions below 7 pprn a decrease is observed in the signal as the concentration of coenzyme increases, because this increase favours the non-inhibited enzymic reaction, such that the increase in absorbance tends towards zero. As can be seen in Fig. 2, for. Hg" concentrations above 7 ppm, on increasing the concentration of enzyme in the solution, the value of the analytical signal (AA) also increases, which shows that the inhibitory effect becomes 0.1 0 10.0 20.0 [Enzyme] mg per 50 ml Fig.2 Effect of concentration of enzyme for different concentrations of Hg". Ethanol, 393 ppm in pyrophosphate buffer; coenzyme, 48 mg dl-1; pH. 8.7; and concentration of enzyme variable between 2 and 40 mg dl-1. Mercury concentrations: A, 2.0; B, 3.0; C, 4.0; D, 5.0; E, 6.0; F, 7.0; G, 8.0; H, 10.0; I, 12.5; and J, 15.0 ppm 0.4 0 / . " 20.0 Fig. 3 Variation of increase in absorbance as a function of Hg" concentration for different concentrations of ethanol. Enzyme, 20 mg dl-1; coenzyme, 48 mg dl-1 of pyrophosphate buffer: and pH, 8.7. Ethanol concentration: A, 55; B, 118; C, 196; D, 300; and E , 500 ppm more pronounced (in absolute terms) as the rate of the non-inhibited reaction increases. For each concentration of enzyme studied, a point is reached at which the increase in absorbance becomes indepen- dent of the concentration of Hg in the solution, indicating that the reaction kinetics tend towards zero order with respect to this parameter, i.e., the number of active sites blocked is virtually constant, having reached an equilibrium.For Hg concentrations below 7 ppm it can be seen that the increase in absorbance versus the concentration of inhibitor is not uniform, showing that, in order to obtain the maximum analytical signal (maximum inhibition), there must be an optimum concentration of inhibitor in each instance. The slowing in the increase in absorbance, as from a given value of enzyme concentration, can be attributed to a steadily decreasing relative blockage of the active sites. This type of behaviour is consistent with a non-competitive inhibition, as was expected.This led to the choice of enzyme concentrations as a function of the Hg" concentrations in the particular sample to be analysed. The analytical signal AA reaches a constant value that is independent of the concentration of Hg in solution for each substrate concentration studied (Fig. 3).ANALYST, MAY 1992, VOL. 117 923 n u I ,u -A I 0 1 .o 2.0 3.0 L reactor/m Fig. 4 Effect of reactor length for different concentrations of mercury. Enzyme, 40 mg dl-1; coenzyme, 80 mg dl-1: H, 8.7; and ethanol concentration, 1000 ppm. Concentration of Hg': A, 2.0; B, 4.0; C, 5.0; and D, 6.0 ppm The value of the inhibitory (Hg) concentration at which the maximum rate of reaction is achieved depends on the concentration of substrate and increases parallel to the increase in the latter concentration.For lower amounts of Hg", the reaction rate is proportional to the concentration of inhibitor. In general, throughout the concentration range of Hg" studied, AA increases parallel to the increase in substrate concentration, tending toward constant values. This shows that in each instance there is a point after which inhibition does not progress, which is the type of behaviour expected for non-competitive inhibition. The possibility of carrying out determinations of Hg at concentrations below 1 ppm prompted a study of the effect of the concentration of ethanol for lower values of enzyme (10 mg dl-1) and coenzyme (24 mg dl-I), a zone which, as mentioned earlier, had been observed to be more favourable for this.In no instance was a detectable analytical signal observed for Hg concentrations below 0.5 ppm. The results obtained led to the use of the corresponding calibrations with substrate concentrations always as a function of the concentration range of Hg" in the samples to be analysed. Reactor length For a reaction characterized by slow kinetics, reactor length, in general, increases in parallel with the residence time. However, as the reactor length is increased, dispersion also increases such that it is necessary to reach a compromise between both parameters in order to improve the sensitivity of the determination. The results obtained (Fig. 4) point to the following: with respect to the analytical signal, this increases until an optimum length is reached because the time of reaction also increases.Thereafter, a decrease in the signal is observed, because of the predominance of physical dispersion over the reaction kin- etics. These results, to a certain extent, differ from those expected, according to the literature concerning this type of reaction when carried out by classical methods.12 In all the procedures used for the determination of metal ions, based on the inhibitory effect of enzymic reactions, long incubation times are required, thus making such determinations tedious and time consuming; this can be avoided by the flow system proposed here. Volume of sample injected This can affect both the magnitude of the signal and its shape. The results indicate, as expected, that the larger the volume injected, the larger the bandwidth, leading to reduced sampling rates.Moreover, on increasing the injection volume, physical dispersion decreases (less dilution) such that, by Table 1 Comparison of results Mercury found/mg ] - I * Mercury FI Dit hizone 2.1 2.1 2.0 5.2 5.3 5.2 7.4 7.5 7.3 10.2 10.1 10.1 14.3 14.4 14.2 method added/mg 1- method * Mean value of three determinations. keeping the chemical variables of the system constant, the analytical signal is greater. Injection volumes of the order of 126 pl lead to a suitable analytical signal without an excessive consumption of sample and with an adequate sampling rate. Flow rate This is one of the most important hydrodynamic variables to be considered in an FI determination because it governs the reaction time and the sampling rate.With respect to the analytical signal, this was found to increase with a rise in flow rate; this is logical as dilution is lower. At a certain flow rate, a tendency to reach a given constant value, due to the dilution occurring in the confluence points, is observed (1.0 ml min-1). Calibration and Determination Limits When the concentration of Hg is lower than 8 ppm, the following is advised for use in the carrier channel C1: de-ionized water, introducing into channel C2: ethanol 500 ppm, and in C3 a solution of enzyme (20 mg dl-1) and coenzyme (48 mg dl-I), keeping the flow rate at 1 ml min-l. A helical reactor of 1.25 m and an injection volume of 126 p1 are employed. When the concentration of Hg is above 8 ppm, it is necessary to modify the concentrations of the different species, the best results being obtained when the determina- tion is carried out under the following conditions.De-ionized water is introduced through channel C1 while the carrier channels C2 and C3 are used to introduce ethanol (1000 ppm) and a solution of enzyme (40 mg dl-I) and coenzyme (80 mg dl-I), respectively. The other physical and hydrodynamic characteristics of the system are kept constant. Under these conditions it is possible to determine concen- trations of Hg between 0.5 and 20.0 mg 1-1, the detection limit being 0.5 mg 1-1. The precision of the procedure was measured by analysis of ten aliquots, each containing 5 ppm of Hg for the first calibration and 8 pprn €or the second, relative standard deviations of 1.1 and 1.4%, respectively, being obtained.Under the proposed conditions it was possible to carry out between 120 and 150 determinations per hour. The results obtained were compared with those of the standard dithizone method16 and are summarized in Table 1. The values obtained by the proposed method can be seen to be in good agreement with those of the standard method. Selectivity of the Procedure There are many metal ions that, in principle, might also act as inhibitors of the enzymic reaction. In this sense, Ag, Cd, Cu, Zn and Pb ions; at different concentrations; have been described as inhibitors. For this study, into the flow system designed as ideal for the determination of Hg, solutions of different elements were introduced at concentrations ranging from 1 to 100 ppm.924 ANALYST, MAY 1992, VOL.117 The Ag ion is an important source of interference because its inhibitory effect on the enzymic reaction is similar to that of Hg for low concentrations of Ag, being slightly lower for concentrations above 4 ppm. For the other species studied (Cd, Cu, Zn and Pb), no inhibition reaction was observed to occur, even at concentra- tions of 100 ppm. The different behaviour shown by these elements in FI shows that, compared with classical methods, this technique, owing to its kinetic characteristics (shorter times), could be a method of kinetic differentiation. The fact that the above- mentioned species, which interfere in the classical procedure, are not a source of interference here indicates that, in enzymic processes of this type, there is an authentic selection based on kinetic parameters, although other parameters cannot be ruled out.Conclusion The possibility of working with inhibition reactions in continu- ous-flow systems has been demonstrated. Although the sensitivity of the procedure is poorer than that of the discontinuous method, because one is working with shorter reaction times (unfavourable kinetic conditions for the inter- fering reactions), the selectivity of the method is considerably improved. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 References Keller, H., Naturwissenschaften, 1965, 39, 109. Giang, P. A., and Hall, S. A., Anal. Chem.. 1951, 23, 1830. Kramer, D. N., and Gamson, R. M., Anal. Chem., 1957, 29, 21A. Hobom, G., and Zollner, N., Z. Physiol. Chem., 1964, 335, 117. Goldstein, J. L., and Swain, T., Physiol. Chem., 1965, 4. 185. Baum, P., and Czok, R., Biochem. Z . , 1959,332, 121. Townshend, A., and Vaughan, A., Talanta, 1970, 17,289. Townshend, A., and Vaughan, A., Talanta, 1969, 16, 929. Mealor, D., and Townshend, A., Talanta, 1968, 15,747. Mealor, D., and Townshend, A., Talanta, 1968, 15, 1371. Mealor, D., and Townshend, A., Talanta, 1968, 15, 1477. Townshend, A., and Vaughan, A., Talanta. 1970, 17, 299. Ruz, J., Luque de Castro, M. D., and Valcircel, M.. Analyst, 1987, 112,259. Fernindez, A., Luque de Castro, M. D., and Valcarcel, M., Fresenius’ Z. Anal. Chem., 1987, 327, 552. Lazaro, F., Luque de Castro, M. D., and Valcarcel. M., Anal. Chem., 1987,59. 1859. Analytical Methods Committee, Analyst, 1965, 90, 515. Paper 1 l02227J Received May 13, 1991 Accepted October 22, 1991

ISSN:0003-2654    

DOI:10.1039/AN9921700921

出版商:RSC    

年代:1992

数据来源: RSC

摘要:

ANALYST, MAY 1992, VOL. 117 925 Determination of N-Acetylcysteine in Pharmaceutical Samples by Flow Inject ion Concepcion Sanchez-Pedreno, Ma. Isabel Al bero, M a . Soledad Garcia and Vicente Rodenas Department of Analytical Chemistry, Faculty of Science, University of Murcia, 30071 Murcia, Spain Two flow injection (FI) methods, involving spectrophotometric detection, are proposed for the determination of N-acetylcysteine (NAC). Both methods are based on the formation of a yellow complex between NAC and Pd" in a medium of 1 rnol dm-3 HCI. In the first method, which is based on the conventional FI technique, NAC is determined over the range 5 x 10-5-5 x 10-3 rnol dm-3, and in the second, in which the doublet-peak FI mode is used, the working range is extended (5 x 10-5-5 x 10-2 rnol dm-3).The FI methods were applied to the determination of NAC in pharmaceutical samples. Keywords: N-Acetylc ysteine; palladium(ii); flow injection; pharmaceutical samples N-Acetyl-L-cysteine (NAC) is a biologically active substance with a mucolytic effect,' shown to be effective as an antidote in cases of acetaminophen poisoning.2 In addition, it is useful in the prevention, o r reduction, of the side effects of cyclophos- phamide treatment in cancer patients.1 Studies on the stability of NAC in pharmaceuticals have shown that this compound is stable at room temperature.3.4 N-Acetylcysteine has been determined by chromatographic,5-9 spectrophotometric*O-*4 and spectrofluorimetric techniques.15 It has also recently been determined by kinetic16.17 and flow injection (FI) methods.18 Two simple, fast and inexpensive methods, useful for the routine determination of the drug in pharmaceuticals and based on the reaction of NAC and PdCI2 and involving FI, are described in this paper. The peak height and width are used as quantitative parameters. Experimental Apparatus The FI system consisted of a Gilson HP4 peristaltic pump (Worthington, OH, USA), an Omnifit injection valve (New York, USA), a Hellma 18 yl flow cell (Jamaica, NY, USA) and a Pye Unicam spectrophotometer (Cambridge, UK) as detector. Connecting tubing of 0.5 mm bore, v l y - (tetrafluoroethylene) (PTFE) tubing and various end-fittings and connectors (Omnifit) were used. For the peak-width measurements, a gradient tube consisting of a Perspex tube of 2 mm i.d.was used. RePgeRts All chemicals were of analytical-reagent grade and the solutions were prepared with doubly distilled water. Stock NA C solution (0.1 rnol dm-3). Prepared by dissolving 1.6319 g of NAC (Merck, Darmstadt, Germany) in 100 ml of water and storing at approximately 4 "C in a dark bottle. Working solutions of NAC were prepared daily by dilution of the stock solution. Palladium dichloride standard solution (5 x 10-3 rnol dm-3). Prepared by dissolving 0.2216 g of PdCI2 (Merck) in 5 ml of water, to which 0.5 ml of concentrated HC1 had been added, by warming the mixture in a water-bath. The solution was cooled and diluted with water in a 250 ml calibrated flask, and titrated as described elsewhere.19 More dilute solutions were obtained by appropriate dilution with water.Hydrochloric acid (6 rnol dm-3). Prepared by dilution of the concentrated acid. Britton-Robinson buffer solutions. These covered the pH range 2.00-8.00. FI Procedures Use the FI manifold shown in Fig. l ( a ) . Inject 70 yl of NAC solution into 5 X 10-4 rnol dm-3 PdC12 in a 1 rnol dm-3 HCI stream and measure the peak height at 380 nm. Prepare a calibration graph by plotting the peak height ( h ) versus NAC concentration over the range 5 X 10-5-5 x 10-3 rnol dm-3. For the peak-width method, use the FI manifold shown in Fig. l ( b ) . Inject 680 yl of NAC solution, with concentrations between 5 x 10-5 and 5 x 10-2 rnol dm-3, into 2 x 10-4 rnol dm-3 PdC12 in a 1 rnol dm-3 HCI stream and monitor the absorbance at 380 nm. Obtain a calibration graph by plotting the time interval between the doublet peaks ( A t ) versus the logarithm of the NAC concentration (In c ) .Determination of NAC in Pharmaceutical Samples No sample pre-treatment was needed for these analyses. Dissolve an accurately weighed or measured volume of the pharmaceutical sample with water, up to 250 ml, in a calibrated flask. Filter, dilute the filtrate, if necessary, and analyse a suitable aliquot by the FI procedures. n Sample 1 I I \ I \ A 380nm . - . . . U 9 = 1.2 mi min-' W n Sample 1 u v,=s80p' 9 = 1.2 ml min-1 W Fig. 1 F1 manifolds for the determination of NAC. (a) Peak-height method: R = reagent solution, 5 x mol dm-3 Pd" in 1 mol dm-3 HCl. (b) Doublet-peak FI mode: R = reagent solution, 2 x mol dm-3 Pd" in 1 rnol dm-3 HCl. Vi = volume injected (loop size); I = length of reaction coil; and q = flow rate (pump)926 110 E E .P 100 22 r r Y lu 0.90 120 I 1 - - - ANALYST, MAY 1992, VOL. 117 80 I I I I 20 40 60 80 100 120 Vi/pl 1 I 1 I 1 1 0.5 1.5 2.5 3.5 4.5 5.5 I/m 1 I 1 1 I 1 0.2 0.6 1 .o 1.4 1.8 2.2 q/ml min-1 Fig. 2 Effect of A, loop size (VJ; B, reactor length ( I ) ; and C, pumping rate ( q ) , on the peak height. Sample injected, 2 x rnol dm-3 NAC Results and Discussion Palladium(1r) chloride reacts with NAC to form a yellow complex.14 In the acidic medium used in this work, it has been ascertained that the complex has a stoichiometric ratio of NAC : Pd" of 2 : 1 and a well-defined absorption maximum at 380 nm. The NAC does not absorb at this wavelength, and PdC12 has a very low absorbance under the same experimental conditions.The reaction between Pd" and NAC has been adapted in order to develop two spectrophotometric-FI methods for determining the drug. FI Method The design of the manifold shown in Fig. l(a) is simple. The sample is injected into the stream of PdC12 solution in 1 rnol dm-3 HCI. The Pd" forms the NAC : Pd" complex, the absorbance of which is measured by means of the detector at 380 nm. In the absence of NAC (blank), a small signal is obtained. This signal is used to pre-adjust the zero absorbance in the detector. The presence of the drug causes an increase in the analytical signal, proportional to its concentration. The optimization of FI and chemical variables was studied in order to establish an FI method. Fig.2 shows the effect of the loop size, the reactor length and the flow rate on the peak height. An increase in loop size produces an increase in peak height (Fig. 2, A); however, at large injected volumes, split peaks were observed. Hence, a loop size of 70 p1 was chosen. The influence of reactor length was studied from the minimum distance possible (injection valve-detector) up to 5 m. The results (Fig. 2, B) showed that the peak height decreases as the reactor length increases. In order to confirm the optimum reactor size, different calibration graphs for NAC with different reactor lengths were produced. A 3 m reactor was selected as this provided the greatest reprodu- cibility. The effect of flow rate on peak height was studied over the range 0.7-2.3 ml min-1. An increase in the flow rate resulted in an increase in absorbance (Fig.2, C). However, this effect was lower between 1 and 2.3 ml min-1, and hence a flow rate of 1.3 ml min-1 was selected. 25 I 1 0 0.5 1 .o 1.5 [PdCI2]/1O3 rnol dm-3 Fig. 3 Effect of Pd" concentration on peak height From the above, the optimum values for the FI variables were as follows: injected volume, 70 pl; reactor length, 3 m ( i d . 0.5 mm); and pumping rate, 1.3 ml min-1. It is known that, in neutral or slightly acidic solution, Pd" ions yield coloured complexes with a number of compounds. In strongly acidic solution, however, the reaction is much more specific for compounds containing sulfur,20 as is found with NAC. For this reason, a strongly acidic medium was selected, the best results being obtained with 1 rnol dm-3 HCI.The influence of the concentration of Pd" was studied in the range 5 x 10-5-1.5 x 10-3 rnol dm-3 and a fixed concentra- tion of NAC of 5 X 10-4 rnol dm-3. As can be observed from Fig. 3, constant and maximum values of peak heights are obtained with Pd" concentrations up to 4 X 10-4 rnol dm-3. A concentration of 5 X 10-4 rnol dm-3 PdC12 was selected, which is sufficient for the total formation of the complex in the range of the calibration graph for NAC determination. Determination of NAC With the described manifold and under the optimum experimental conditions (5 x rnol dm-3 PdCI2 and 1 rnol dm-3 HCI), a calibration graph linear between 5 x 10-5 and 5 x 10-3 mol dm-3 NAC was obtained. The regression equation found was h = 104.9 X 103[NAC] + 37.6, where h is the peak height in millimetres and [NAC] is expressed in rnol dm-3, with a correlation coefficient of 0.9995.The relative standard deviation (RSD) for ten determinations of 4 x 10-4 mol dm-3 NAC was 1.4%. The detection limit was 1 x 10-5 mol dm-3 NAC and the sampling frequency was 45 h-1. Doublet-peak FI Mode The most commonly used quantitative parameter in FI is the peak height. However, it is also possible to obtain useful analytical information from other properties of the response curve, but little use has been made of peak area, although its usefulness in some situations has been demonstrated.21 The use of peak width as a quantitative parameter in FI was demonstrated by RfiiiCka et al.22 and has been applied by several workers.23-26 Doublet peaks are obtained when the operating variables are adjusted so that the injected sample material is in excess over the reagent in the centre of the reaction zone.Tyson27JS proposed equations relating the time interval between the peaks and the concentration of the material injected. The major advantage of this FI monitoring mode is the consider- able extension of the working concentration range by several orders of magnitude. This increase is originated by the generation of an exponential concentration gradient of the sample and reagent, which is responsible for the appearance of doublet peaks.27 Therefore, the time interval ( A t ) between theANALYST, MAY 1992, VOL. 117 80 60 v) ‘i; 40 20 927 - - - - d 01 I I I 1 I 200 400 600 800 1000 1200 Vil$ I I I I 1 I 1 0 200 400 600 800 1000 v/p I 0.5 1 .o 1.5 2.0 2.5 3.0 qlml min-l Fig.4 Variation of At with: A. the volume of sample injected (V,); B, volume of the gradient tube ( V ) ; and C, pumping rate (4). Sample injected, 5 x 10-4 rnol dm-3 NAC doublet peaks is related to the logarithm of the sample concentration. One of the problems found in routine analytical determina- tions is that the analyte concentrations of the sample often do not fall within the limited range of concentration of the calibration graphs. As the routine determination of NAC is the aim of this work, the peak-width (separation between doublets) FI method was applied in order to extend the useful working range for this drug. Hence, a greater loop size and an injected sample concentration greater than the reagent carrier-stream concentration were used, and a short connect- ing line was introduced to produce the appearance of doublet peaks.A logarithmic relationship between the time interval between the doublet peaks and the concentration of the injected sample was obtained. The effect of the experimental variables on At was studied. The results obtained are shown in Fig. 4. The optimum values for the FI variables are as follows: q = 1.2 ml min-1, with which a suitable separation between the peaks without a notable decrease in the sampling frequency is obtained; Vi = 680 p1, the large sample volume injected ensures that doublet peaks are obtained; several tubes of 2 mm i.d. and between 0 and 40 cm long were used for the study of the influence of the gradient tube volume on At.The distance between the doublet peaks decreases when the volume of the tube increases, as is shown in Fig. 4, B. Hence, a tube of 0.5 mm i.d. with the minimum possible length was used to connect the injection valve and the detector. In this way, maximum separation between the peaks was obtained. The concentrations of some reagents are decisive. Hence, the optimum concentration of PdCI2 is 2 x 10-4 rnol dm-3, which produces well-defined doublet peaks. The acidic medium selected was HCI (1 rnol dm-3). Calibration Graphs The equation of the calibration graph for the determination of NAC is At = l.Sln[NAC] + 31.8 ( r = 0.9986), where At is expressed in seconds and [NAC] in rnol dm-3. The equation is satisfied between 5 x 10-5 and 5 x 10-2 rnol dm-3 NAC. Therefore, by using the peak width as a quantitative parameter, it is possible to extend the calibration graph for the routine determination of NAC by ten orders of concentration.The RSD (n = 10) for 5 x 10-4 rnol dm-3 NAC was 3.4%. Table 1 Effect of various foreign species on the determination of 2 X rnol dm-3 NAC by the two FI methods Foreign species Maximum tolerated [species] : [NAC-] molar ratio S042-, NO3-. F-, Cz042-. lactose 200* C03*-, alanine, aspartic acid, arginine, asparagine, valine, glutamine. proline, glycine, lysine, glutamic acid, leucine, saccharin, fructose, glucose, caffeine, tartrate, citrate 100 Phenylalanine, Br-, maltose 50 Histidine, tryptophan 25 Tyrosine, starch? 10 N , N’-Diacetylcystine 6 Methionine 0.1 * Maximum molar ratio tested.Mass ratio. Table 2 Determination of NAC in pharmaceutical preparations. Composition of samples. Fluimicil: 100 mg NAC, 8 mg saccharin and excipient up to 5 g; Flubiotic: 250 mg amoxycillin (trihydrate), 100 mg NAC, 4 mg saccharin and excipient up to 5 g; Fluimicil ampoules: 300 mg NAC in 3 ml of solution at pH 6.5; Rinofluimucil: 10 mg NAC. 5 mg 2-heptylamine sulfate, 0.125 mg benzalkonium chloride and excipient up to 1 ml NAC content FI peak- Doublet-peak Certified Trade name* height method FI mode value Fluimicil 19.9 k 0.27 20.5 k 0.5t 20 mg g-1 Flubiotic 19.8 k 0.2t 19.6 k 0.6t 20mgg-I Fluimicil ampoules 98.6 k 0.1$ 98.2 k 0.4$ 100 mg ml-* Rinofluimucil 9.7 k 0.3$ 9.8 k 0.51: 10 mg ml-1 * All preparations manufactured by Zambon, Barcelona, Spain.t mg g-* (-t RSD). 1: mg ml-1 (kRSD). Study of Interferents in Each Method The effect of foreign species in both FI methods was studied. The results for the determination of 2 x 10-4 rnol dm-3 NAC are listed in Table 1. The tolerance limit was taken as the concentration causing an error of not more than k5% in the determination of NAC. As can be seen, the proposed methods are sufficiently selective. Applications The two proposed FI methods were applied to the determina- tion of NAC in various pharmaceutical products. No sample pre-treatment was required for the determination of NAC, apart from suitable dilution. The results obtained are pre- sented in Table 2. There are no significant differences between the certified values and those obtained by the two proposed FI methods.The authors are grateful to the Spanish Direccion General de Investigacion Cientifica y Tecnica (DGICYT) (Project 87- 0053) for financial support. References 1 The Pharmacological Basis of Therapeutics, eds. Goodman, G. A., Goodman, L. S., Rall. T. W., and Murad, F., Panamericana, Madrid, 7th edn., 1989, p. 911 (in Spanish).928 ANALYST, MAY 1992, VOL. 117 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Prescott, L. F., illingworth, R. N., Critchley, J. A., Stewart, M. J., Adam, R. D., and Proudfoot, A. T., Br. Med. J., 1979,2, 1097. van Loenen, A. C., de Jong, A., van der Meer, Y. G., and Schwietert, H. R., Pharm. Weekbl., 1985, 120, 313. Vythg, A., and Timmer, J. G., Pharm. Weekbl., 1985,120,444. Shimada, K., Tanaka, M., and Mambera. T., Anal.Chim. Acta, 1983, 147, 375. Toyo'oka, T., and Imai, K., J. Chromatogr., 1983, 282, 495. Lewis, P. A., Woodward, A. J., and Maddock, J., J. Pharm. Sci., 1984, 73, 996. Holdiness, M. R., Morgan, L., Gillen, L., and Harrison, E., J. Chromatogr., Biomed. Appl., 1986, 55, 99. Johansson, M., and Westerlund, D., J. Chromatogr., 1987,385, 343. Raggi, M. A., Cavrini, V., and Di Pietra, A. M., J. Pharm. Sci., 1982, 71, 1384. Talley, J. R., Magarian, R., and Sommers, E., Am. J. Hosp. Pharm., 1973, 30, 526. Murty, B. S. R., Kapoor, J. N., and Kim, M. W., Am. J. Hosp. Pharm., 1977, 34, 305. Groszkowski, S.. and Ochocki, Z., Farm. Pol., 1980, 36, 273. JovanoviC, T. S., and StankoviC, B. S., Analyst, 1989, 114,401. Imai, K., Toyo'oka, T., and Watanabe, Y., Anal. Biochem., 1983, 128, 471. 16 17 18 19 20 21 22 23 24 25 26 27 28 Garcia, M. S., Sinchez-Pedreiio, C., and Albero, M. I., Analyst, 1990, 115, 989. Viiias, P., Hernandez Cordoba, M., and Sanchez-Pedrefio, C., Analyst, 1990, 115, 757. Viiias, P., Sinchez, J., and Hernandez, M., Quim. Anal., 1990, 9, 205. Vogel, A., Quantitative Inorganic Analysis, Longman, London, 3rd edn., 1961. Akerfeldt, S., and Lovgren, G., Anal. Biochem., 1964, 8,223. Wolf, W. R., and Stewart, V. K., Anal. Chem., 1979, 51, 1201. RGiiCka, J., Hansen, E. H., and Mosbaek, H., Anal. Chim. Acta, 1977.92, 235. Pardue, H. L., and Fields, B., Anal. Chim. Acta, 1981,124,39. Olsen, S., RfiiiCka, J., and Hansen, E. H., Anal. Chim. Acta, 1982, 136, 101. Stewart, K., and Rosenfeld, A., Anal. Chem., 1982, 54.2368. Tyson, J. F., Analyst, 1984, 109, 319. Tyson, J. F., Anal. Chim. Acta, 1986, 179, 131. Tyson, J. F., Analyst, 1987. 112, 523. Paper I lO4757D Received September 13, 1991 Accepted November 19, 1991

ISSN:0003-2654    

DOI:10.1039/AN9921700925

出版商:RSC    

年代:1992

数据来源: RSC

摘要:

ANALYST, MAY 1992, VOL. 117 929 BOOK REVIEWS chemometric techniques might be applicable to his or her work then this collection of tutorials represents a good starting place. Stephen J. Haswell C hem o met r ics Tutor ia Is Edited by D. L. Massart, R. G. Brereton, R. E. Dessy, P. K. Hopke, C. H. Spiegelman and W. Wegscheider. Collected from Chemometrics and Intelligent Laboratory Systems -An International Journal, Volumes 1-5. Pp. vii + 427. Elsevier. 1990. Price $66.75; Dfll30.00. ISBN 0-444- 88837-3. This text represents a compilation of tutorial papers that have appeared in the journal Chemometrics and Intelligent Laboratory Systems since 1986 and cover the main subject areas of the discipline. For those not familiar with the journal the tutorial papers are for me one of the outstanding features of that publication and the book therefore represents a comprehensive tutorial-type guide to the subject presented by experienced chemometricians.The inevitable independence or stand-alone nature of each tutorial results in the book having little or no co-ordination except for a contents page and a subject index. However, each of the 27 chapters represents a concise and critical review of its particular subject but some overlap between tutorials does occur, especially in the introductory paragraphs. All of the tutorials (Chapter 27 is a review rather than a tutorial) have their own contents list, and are, in general, written in a lucid manner with the use of good worked examples. There is some variation in the level at which each of the tutorials is pitched but for the sections of particular interest to the analyst this will not cause a problem for a novice to the subject.The chapters have been roughly combined into subject groups and a general list of contents is present at the front of the book to guide the reader. I have reviewed the book very much with a bias towards the analytical chemist and so found some chapters of little direct relevance. The early chapters offer an introduction to the use of computers in the laboratory and Chapter 1, on scientific word processing, I found of particular value, with Chapter 2 on LIMS infrastruc- ture being undoubtedly of interest to many analysts. The following five chapters take the reader deeply into expert systems and computer programming describing the Dendral project and the use of PROLOG.This latter subject covered in Chapters 6 and 7 will be of value to those interested in expert systems. For the analytical chemist the real interest in the book starts with Chapters 8-11 on experimental design and optimization with tutorials on ANOVA, factorial design, and simplex with two specific tutorials (Chapters 10 and 11) on applications in HPLC. The next two tutorials (or chapters) address the area of signal processing, whilst Chapter 14 focuses on sampling theory. The final group of chapters (15-26) offer the reader a substantial literature base in multivariate and related methods. These chapters vary in style, length and mathematical regime but cover all the techniques widely used including principal component analy- sis, correspondence factor analyses and spectral map analysis with Chapter 19 offering a good comparison between these methods.Regression techniques are represented in detail along with projection techniques, with the final few chapters describing the use of multivariate techniques in the area of geoscience. The final chapter is a review of ‘fuzzy theory’ but it will not assist those readers confused by the extensive subject coverage given in the preceding 26 chapters! The book represents an excellent source of information for a wide range of chemometric techniques of great relevance to any analytical chemist. However, the text could not be described as easy bed-time reading, but each tutorial, when taken in its own right, represents a complete tutorial on its specific subject area.For the analyst who wishes to see how Multielement Detection Systems for Spectrochemical Analysis By Kenneth W. Busch and Marianna A. Busch. Volume 107 in Chemical Analysis. A Series of Monographs on Analytical Chemistry and Its Applications. Pp. xxi + 688. Wiley-lnterscience. 1990. Price f70.00. ISBN 0-471 -81 974- 3. Multi-element detection systems for optical spectroscopy have historically been the recipients of considerable research effort. A large variety of instrument systems has appeared, each designed to provide multi-element determinations based on a variety of sources, optics, detectors and spectroscopic prin- ciples. The stated purpose of this book is a unified treatment of the fundamental principles necessary for understanding this spectroscopic instrumentation and a comprehensive discus- sion of modern image detectors.It is intended for the graduate student in analytical spectroscopy and researchers in other disciplines. The book is divided into three sections. After an introduc- tory chapter, Chapters 2-7 are devoted to the principles of optics, diffraction, spectrographs and spectrometers, and Hadamard and Fourier transform spectroscopy. Chapters 8-1 1 focus on photographic, photoelectric and solid-state detectors. Finally, Chapters 12-15 take a look at multi- element detection systems. Chapter 12 provides an interesting discussion on the philosophy of instrument development. Chapter 13 then provides a brief overview of atomic emission, absorption and fluorescence spectrometry with consideration of the possible dominant noise sources.Chapters 14 and 15 review various commercial and research detection systems under the heading of transform and non-transform systems, respectively. The authors have succeeded very nicely in their stated purpose for this book. They have drawn together, in a single text, the many fundamental areas that are necessary for research in the field of analytical spectroscopy. The book is very readable, serves as an excellent reference source for research in the field, and provides numerous historical accounts, which provide an interesting perspective. The principles of optics, diffraction, spectrometers and inter- ference are presented in a very understandable manner without a blizzard of mathematical equations.The review of solid-state detectors and underlying principles is very detailed. Radiation sources are discussed only in the abstract as sources of various limiting noises. The effects of these types of noise are then considered with respect to the instrumental design. The coverage of transform spectrometric methods is par- ticularly well done. The groundwork is well laid with chapters on interference, masked spectrometers and Fourier transform spectroscopy. Chapter 14 then presents a detailed review of the state-of-the-art and the limitations of the field as based on consideration of signal-to-noise ratios arising from the various sources. The one weakness I found with the book was in the review of non-transform detector systems (Chapter 15). Compared with the preceding chapter on transform spectrometric systems, the review of non-transform systems seemed rushed and did not provide the same detailed coverage.Of course, non-transform systems cover a much wider field of designs and sources. The same depth of coverage would have made for a longer book (which is already 688 pages). It is regrettable, however, that the authors did not provide a more thorough930 ANALYST, MAY 1992, VOL. 117 evaluation of these systems, especially since they did such a superb job on transform methods. Still, the strengths of this book far outweigh this weakness. It is a welcome addition to any spectroscopists’ library. J . M . Harnly DECHEMA Corrosion Handbook. Volume 6. Acetic Acid, Alkanols, Benzene and Benzene Homologues, Hydrogen Chloride Edited by Dieter Behrens.Pp. ix + 368. VCH. 1990. Price DM775.00 and f286.00 (Single volume price); DM645.00 and f238.00 (Subscription price). ISBN 3-527-26657-7 (VCH Verlagsgesellschaft); 0-89573-627-6 (VCH pub- lishers). Having reviewed earlier volumes in this series, this latest contribution maintains the standards set by the editors. For new readers, the editors’ aims are to review the effects of corrosive media on metallic materials, non-metallic inorganic materials, organic materials, and materials with special properties, and to provide answers to the questions designers, corrosion specialists and others want. Considerable detail is given so that questions beyond the behaviour of a material under consideration can be answered, and possible protective measures and the conditions under which a less resistant material will give satisfactory service can be considered.Volume 6 commences with 175 pages devoted to acetic acid (the remaining sections on alkanols, benzene and benzene homologues, and hydrogen chloride are each around 50 pages long). The interaction of acetic acid, from vinegar to glacial, with different materials is preceded by an interesting and detailed account of the various industrial procedures for preparing acetic acid. I was intrigued to observe that the reference numbers began sequentially but soon numbers above 762 appeared and thus felt the urge to try a minor detective-type investigation. A survey of the 848 references revealed that only two before reference 763 were to work done after 1978.I thus deduced that this chapter was originally written around 1979, and as the latest reference is to 1988, was extended about ten years later, but without altering the original reference numbering. As the later information does not, unlike research papers, modify the earlier conclusions the insertions are either new data or amplify the existing data, and consequently the narrative reads smoothly. Formic acid, also as a special topic, and the alkanecarb- oxylic acids (propionic and higher acids) were covered in Volume 4, and hence the account of the carboxylic acids is now complete. Volume 4 also included the polyols, and now the addition of the monohydric alcohols would make the alkanol story complete, except that methanol is only here mentioned occasionally for comparison: perhaps it will be discussed in a future volume.Here, mainly ethanol, propanol and butanol are described, including air-alcohol mixtures, aqueous mix- tures and the addition of small amounts of HCI to the latter to achieve passivation. The effect of these and other mixtures on stress corrosion cracking and on polymers and resins is also reported. The latest references are in 1986. Hydrochloric acid was reported in Volume 5 and now hydrogen chloride gas completes this story. The value of this chapter, to my mind, is the detail provided for dry hydrogen chloride (gas and liquid), which does not attack many metals and alloys, and the harmful effects of trace amounts of moisture. Under the latter circumstances the need to keep temperatures above the dew-point of the system is stressed, to avoid corrosion. Suitable coatings and linings are also described. As with the acetic acid chapter this one appears to have been written some years ago but then updated with references up to 1989. The chapter on Benzene and Benzene Homologues is the first in this series dealing with aromatic materials. Pure benzene does not attack most metals, but with technical-grade or crude benzene, particularly if sulfur is present, attack can occur. Benzene is frequently the most aggressive agent of the aromatic hydrocarbons towards organic materials. It is thus useful to learn which resins and other synthetic materials are resistant to, or swell in, benzene and its homologues. Interestingly the earliest reference is 1970 and the latest 1987. This volume of the DECHEMA Corrosion Handbook is therefore recommended, and necessary if you (or more likely your library) have previous volumes, as it completes the survey of the corrosive effects of acids and alcohols. T. R. Griffiths

ISSN:0003-2654    

DOI:10.1039/AN9921700929

出版商:RSC    

年代:1992

数据来源: RSC

摘要:

ANALYST, M.4Y 1992, VOL. 117 93 1 CUMULATIVE AUTHOR INDEX JANUARY-MAY 1992 Aarkrog, Asker, 497 Abdel-Hay, Mohamed H.. 157 Abildtrup, Anne, 677 Abuirjeie, Mustafa A.. 157 Aguilar Gallardo. A., 195 Alarabi. Hosen, 407 Albero, M;‘. Isabel, 925 Alder. John F., 899 Ali, Zulfiqur, 899 Almendral Parra, M. Jesus, 921 Alonso Mateos. Angel, 921 Analytical Methods Committee Angeli, Gyorgy Z . , 379 Anglov, B., 419 Aras. Namik K., 447 Axelsson, H.. 417 Aydin, Hasan, 43 Bahari, M. Shahru, 701 Balamtsarashvili, Gyorgy M.. Ballesteros, L., 539 Barary, Magda H., 785 Barclay, David, 117 Barefoot, Ronald R., 563 Barek, Jiii, 751 Barnett, Catherine L., 505 Baronciani, Dante. 511 Barros, Flavio Guimariies, 917 Batrakov, G. F.. 813 Baumann, Elizabeth W., 913 Baumgartner, Dieter, 475 Baxter. Douglas C., 657 Beckmann, Christiane.525 Behne, Dietrich, 555 Beltyukova, Svetlana V., 807 Beresford, Nicholas A., 505 Bermond. Alain, 685 Bersier. Pierre M., 863 Berzero. Antonella, 533 Bicanic, Dane D., 379 Bicker, Gary, 767 Bjornstad, Helge E., 435, 439, 515. 529, 619 Blaauw, Menno, 431 Bond, Alan M., 857 Bondarenko, lgor I . , 795,803 Bonet Domingo, Emilio, 843 Boomer, Dave, 19 Borisov, A. P., 813 Borroni. Pier Angelo, 533 Bourgeois. Serge, 685 Bourgoin. Bernard P.. 19 Brenes, Manuel, 173 Bretten. S . , 501 Brindle, Ian D., 407 Brittain, John E., 515 Bulska, Ewa, 657 Bunzl, K., 469 Burgess, John, 605 Butler, L. R . P.. 230 Byrne. Anthony R., 251. 443, Cacho, Juan, 31 Cai. Pei Xiang, 185 Campbell, Milford B., 121 Campos Venuti. Gloria, 511 Chai. Fong, 161 Chan, Wing Hong, 185 Chang.Xi-jun. 145 Chattaraj, Sarnath, 413 Chau, Y. K.. 571 Chaudhry, Muhammad Mansha. Chen. Hengwu, 407 Cheng, Oi-Ming. 777 Chenieux. Jean-Claude, 77 Chiu. Teresa P. Y . , 777 Christensen, Jytte M., 419, 677 Chudinovskyh, T. A., 813 Clark. David, 863 Coker. Raymond D., 67 97, 817 807 665 713 Colbert, David L.. 697 Colgan, Peter A., 461 Colina de Vargas, Marinela, 645 Cornelis. Rita, 583 Corns, Warren T., 717 Coulter, Brian, 521 Coxon, Ruth E., 697 Craig, Peter J., 823 Crespi, Vera Caramella, 533 Crews, Helen M.. 649 Criddle, W. J., 701 Cunha, Ildenise B. S. . 905 Cunningham, John D., 521 Das, Arabinda K., 413 Das, Pradip K.. 791 Davey, David E., 761 Dawson, David E., 461 Day, J. Philip, 619 de Bruin, Marcel, 431 de Ruig. Willem G., 425, 545 Delpueeh, Jean-Jacques, 267 Deng, Y ., 873 Dermelj, M., 443 Dhingra, Surendra Kumar, 889 Diamond. Sean, 521 Dinesan. Maravattiekal K., 61 Doklea, Erika, 681 Donard, Olivier F. X., 823 Duffy, Jarlath T., 521 Ebdon, Les, 717 Edgar, Duart, 19 El-Din, Mohie Sharaf, 157 El-Hallaq. Yasser H.. 447 EI-Yazbi, Fawzy A., 785 Ellingsen, Dag, 657 Emteborg, Hikan, 657 Eremin, Sergei A.. 697 Evans, Don, 19 Faas, Christoph. 525 Fang, Wang, 757 Farrahov, I. T., 813 Ferreira, Vicente, 31 Fichtl, Burckhard, 681 Finster, Ute, 351 Florence, T. Mark, 551 Fogg, Arnold G., 751 Forth, Wolfgang. 681 Frech, Wolfgang. 657 Gaare, E., 501 Gaind, Virindar S . , 9, 161 Gajendragad, M. R. . 203 Games. David E.. 839 Gammelgaard. Bente, 637 Gao, Wen-yun, 145 Garcia Alvarez-Coque, Maria Celia, 831, 843 Garcia, Pedro, 173 Garcia de Marfa, Candido.921 Garcia Sanchez. F., 195 Garmo, Torstein H.. 487, 529 Garrido, Antonio, 173 Gatford, Christopher, 199 Genova, Nicla. 533 Gokmen, Ah. 447 Gokmen, Inci G.. 447 Gomez-Ariza, J . L., 641 Grinberg, Nelv. 767 Haapalainen. Anne, 361 Hall. Tony, 151 Hamalainen, Lea, 623 Haswell, Stephen J., 67, 117 Haugen, Lars E . , 465. 529 He, Qong. 181 Heininger, P., 295 Hempel, Maximilian, 669 Hendrix, James L., 47 Henzel, Norbert, 387 Hercules. David M., 323 Hermecz, I.. 371 Hill, Steve J . , 717 Hintelmann, Holger. 669 Hirayama. Kazuo, 13 Hojker, S . , 443 Holst, Erik, 707 Hori, Toshitaka, 893 Horn, A., 355 Horvat, Milena, 665. 673 Horvath. G . , 371 Houalla, Marwan, 323 Houk, R. S., 577 Hove, Knut, 487 Howard, Brenda J., 505 Hu, Shengshui, 181 Huf, Fred A ., 425 Hughes, Terence C., 857 Hutton, Robert C., 649 Ioannou, Pinelopi C., 877 Ishibashi, Mumio, 727 Jana. Nikhil R., 791 Jansen, A. A. M., 425 Jeran, Z . , 673 Jgns, Ole, 637 Johansson, Sven A. E., 259 Juretid, Dubravka, 141 Kageyama, Susumu, 13 Kalpana, G . , 27 Kanda, Yukio. 883 Kanert, George A., 121 Karpov, V. S . . 813 Karshman, Samir, 407 Kim, Young-Man, 323 Kirchner, Gerald, 475 Kiss, A. I . , 371 Klaeboe, Peter, 335, 351, 355. Kocherlakota, Nirmala, 401 Kocjan, Ryszard, 741 Komarevsky, V. M., 813 Konstantianos, Dimitrios G., 877 KoroSin, Janez. 125 Koshy, Valsamma J . , 27 Koiuh, Nevenka, 125 Kracke, W.. 469 Kravchenko, Tatyana B . , 807 Landon, John, 697 Langmyhr, F. J., 229 Larkins, P. L., 231 Lau, Oi-Wah, 777 Lauer, Jean-Claude, 387 Laurence, Christian, 375 Laurens, Thierry, 387 Le, Xiao-chun, 407 Ledford, Jeffrey S ., 323 Lee, Albert Wai Ming, 185 Leppard, Gary G., 595 Levillain, Pierre, 77 Liebl. Bernhard, 681 Lien, H . , 481 Littlejohn. David, 713 Livens, Francis R., 505 Lu. Jianmin. 35 Lubbers, Marcel, 379 Luk, Shiu-Fai, 777 Luo. Xing-yin, 145 LupSina, V.. 673 Luterotti, Svjetlana. 141 Lydersen, Espen, 613 McAulay, Ian R., 455, 521 MeCalley, David V., 721 McGee. Edward J., 461 MacNeill, Geraldine, 521 Mangels. A. Reed, 559 Margielewski, Leszek, 207 Marshall, Geoffrey B., 899 Martin. Fabienne, 823 Mastryukov, V. S . , 355 Masuda, Akimasa, 869 Matlengiewicz, Marek, 387 Matsumura. Yasuharu, 395 Matsuoka, Shiro, 189 Mayes, Robert W., 505 Mazalov, Lev N.. 795. 803 Medina Hernandez, Maria Jose, 365 831, 843 Mellqvist, J., 417 Meloni, Sandro, 533 Mennie, Darren, 823 Miao-Kang, Shen, 137 Midgley, Derek, 199 Milacit, Radmila.125 Milosavljevid, Emil B., 47 Minhas, Harp, 695 Moeder, Charles, 767 Momin, Saschi A., 83 Montagu, Monique, 77 Morales, E., 641 Moran, Diarmuid, 455, 521 Moreno Cordero, Bernardo, 215 Morikawa, Hidehiro. 131 Moser-Veillon, Phylis B., 559 Miiekter, Harald, 681 Mulcahy, Dennis E., 761 Miirer, Ann J . L., 677 Myrvold. B. O., 355 Nakamura, Toshihiro, 131 Narayana, B., 203 Narayanaswamy, Ramaier, 83 Nawaz, Sadat, 67 Neagle, William, 863 Neddersen, Robert, 577 Nelson, John H., 47 Nerin, Christina, 31 Nibbering, Nico M. M., 289 Nicole, Daniel, 387 Nieboer, Evert, 550 Nielsen, Bent, 637 Nielsen, Claus J., 335, 355, 365 NikoliC, Sneiana D., 47 Norris.John D., 3 Novozamsky, Ivo, 23 Ngren, A., 481 Obokata, Takao, 849 O’Connell, Gregory R., 761 Oddone, Massimo, 533 Ohtani, Hajime, 849 Oka, Hideyuki, 131 Okano, Teruo, 395 O’Keeffe, Ciaran, 461 Olsen, Inge Lise Brink. 707 Ortiz, J.. 539 Ostah, Naman. 823 0stby. Georg, 481, 487 Oughton, Deborah H., 435,481, Owen, Linda M. W., 649 Padalikar. Sudhakar V., 75 Pal, Tarasankar, 791 Pasquini, Celio, 905 Patil, Vitthal B., 75 Patterson, Kristine Y., 559 Peddy, Rao V. C., 27 Pedersen, 0yvind, 529 Perez Pavon, Jose Luis, 215 Perpall, Holly J., 767 Petit-Paly, Genevieve, 77 Petrone, Massimo, 511 Pfund, B. Valentin, 857 Pilipets, L. A., 813 Plambeck, James Alan, 39 Plaza, Stanislaw, 207 Polko, A. B. S . , 613 Porenta, M., 443 Poulsen. Otto M., 677 Powell, Mark J., 19 Preston, Brian, 3 Proctor, Andrew, 323 Purdy.William C.. 177 Pusztay, L.. 371 Qi-Lu, 869 Quinn, Gregory W., 689 Raczynska, Ewa D., 375 Rafferty, Barbara, 461 Raisanen, Marja L., 623 Ramis Ramos, Guillermo, 843 Ransirimal Fernando, Angelo, 515, 619 39932 ANALYST, MAY 1992, VOL. 117 Rao, T. H., 735 Redford. K., 355 Rezvitskii, Victor V., 795, 803 Rideau, Marc, 77 Riise, G., 481 Risica, Serena, 511 Rivikre, J. C., 313 Rocheleau, Marie-JosCe, 177 Rodenas, Vicente, 925 Roepstorff, Peter, 299 Roessner, Frank, 351 Rogani, Antonia, 511 Romero, Romer A., 645 Rosen, A., 417 Ross, Lynn M., 3 Rozas, Leonor G., 921 Rubini, Patrice, 387 Ruiz-Benitez, M., 641 Ruostesuo, Pirkko, 361 Rusterholz, Bruno, 57 Sablinskas, Valdas, 365 Sabri, Suzy M., 785 Sakai, Tadao, 211 Salbu.Brit. 243,435,439,454, Saleh. Hanaa, 87 Salzer, Reiner, 351 Samoshin, V. V., 853 Sanchez-Pedreiio, Concepcion, Sanyal, Asis K., 93 Saraswati, Rajananda, 735 Sato, Jun, 131 481,487, 515, 613,619 925 Scalia, Santo, 839 Schimrnack, W., 469 Schnekenburger, J . , 87 Segal, Michael G., 505 Seiler, Kurt, 57 Selnzs, Tone D. ,493 serradell, V., 539 Sestakov, G., 443 Sevalkar, Murlidhar T., 75 Severin, Dieter, 305 Shpigun, L. K., 853 Shum, Sam C. K., 577 Silbert, Leonard S., 745 Simon, Wilhelm, 57 Singh, Ajai Kumar, 889 Singleton, Diane L., 505 Sinru, Lin, 757 Sipachev, Viktor A., 383 skogland, T., 501 Slejkovec, Z., 443 Smith, David S., 697 Soledad Garcia, Ma., 925 Solov’eva, G. Y., 813 Solyom, Aniko M., 379 Sperling, Michael, 629 Stegnar, P., 443, 673 Steinberg, Karl-Hermann, 351 Steinnes, Eiliv, 243, 454, 501 Stepanets, 0.V., 813 Stockwell, Peter B., 717 Stoeppler, M., 295 strand, Per, 493 Stupar, Janez, 125 Sturgeon, Ralph E., 233 Su, Zhi-Xing, 145 Sugiyama, Masahito, 893 Sultan, Salah M., 773 Siilzle, Detlev, 365 Syed, Akheel A., 61 Tabuchi, Toyohisa, 189 Taha, Ziad, 35 Taira, Masafumi, 883 Taylor, David M., 689 Temminghoff, Erwin J. M., 23 Terao, Tadao, 727 Thomas, C. L. Paul, 899 Thomas. J., 419 Thomas, J . D. R., 701 Thomassen, Yngvar, 229, 657 Torres-Grifol, Juan F., 721 Toyo’oka, Toshimasa. 727 Treiger, Boris A., 795, 803 Tsingarelli, R. D., 853 Tsuge, Shin, 849 Tubino, Matthieu, 917 Tway. Patricia, 767 Unohara, Nobuyuki, 13 van den Berg, Constant M. G. van der Struijs, Teunis D. B., Van Loon. Jon C., 563 van Staden, Jacobus F., 51 Veillon, Claude, 559 Viard, Bernard, 329 Vohra, Kusum, 161 589 545 Wahbi, Abdel-Aziz M., 785 Waidmann, E., 295 Waki, Hirohiko. 189 Walsh. Amanda, 649 Wang, Joseph. 35 Wang, Kemin, 57 Warwick, Peter. 151 Welz, Bernhard, 629 Westerberg, Lars M., 623 Wilken, Rolf-Dieter, 669 Willie, Scott, 19 Winnewisser. Brenda P., 343 Woodgate, Bruce E., 239 Wu. Weh S., 9 Xiulin. Wang, 165 Yahaya, Abdul Hamid, 43 Yano, Tatsuya, 849 Yasuhara, Hisao. 395 Ye, M., 873 Yin, Xuefeng, 629 Yin-Yu, Shi, 137 Yoshimura, Kazuhisa. 189 ZaniC-GrubiSiC, Tihana, 141 Zapolsky, M. E., 853 Zecchini, Pierre, 329 Zefirov. N. S., 853 Zelyonkina, 0. A., 853 Zhan, Guang-yao, 145 Zhao, Zaofan, 181 Zheng, Shaoguang, 407 Zolotov, Yu. A.. 853 Yu, Yu-fu, 439

ISSN:0003-2654    

DOI:10.1039/AN9921700931

出版商:RSC    

年代:1992

数据来源: RSC