摘要:

124 Analyst, February, 1975, Vol. 100,Pp. 124-128 The Titrimetric Determination of Beryllium by Using the Tartrate = Fluoride Procedure N. A. Bell Department of Chemistry and Biology, Shefield Polytechnic, Pond Street, Shefield, S1 1 WB The tartrate - fluoride titrimetric method for the determination of beryllium has been re-investigated and a modified procedure has been developed to allow the determination of beryllium in the presence of other metal ions. The method is stoicheiometric, rapid and precise and is applicable to amounts of beryllium from 0.1 to 16 mg. The effects of diverse ions were investigated and many interferences were eliminated with EDTA. There are many titrimetric methods for the determination of beryllium but most of them are indirect and applicable only to pure salts.Titrimetric methods for determining beryllium have the advantages of rapidity and of eliminating the potential dust hazard associated with gravimetric methods. Such methods have been stated to be the least satisfactory of the chemical methods for beryllium, their reliability not being definable with any certainty,l although the justification for this statement is of doubtful validity. The most widely used titrimetric method is an empirical procedure based on the formation of the very stable tetra- fluoroberyllate ion when fluoride is added to beryllium hydroxide at pH 8.6. The amount of hydroxide ion liberated is proportional to the amount of beryllium present, and is deter- mined with standard a ~ i d . ~ J An alternative titrimetric method, proposed many years ago by ZolotukhinJ4 is based on the liberation of hydroxide ion when a solution of a beryllium tartrate complex, neutral to phenolphthalein, is treated with a potassium fluoride soluton that is also neutral to this indi~ator.~ This method has not found wide acceptance and has therefore been re-investigated in order to assess its value for the determination of beryllium in the presence of other ions.The liberation of hydroxide ion by fluoride, made use of in the most common titrimetric method for beryllium, is not stoicheiometric as the precipitate contains occluded basic salts ; although the method is empirical, it is rapid and a c c ~ r a t e . ~ ~ ~ It has been confirmed that this complication can be eliminated by keeping the beryllium as a soluble basic tartrate complex.4 A graph of the volume of standard acid plotted against milligrams of beryllium over the range from 0.1 to 16-0 mg is rectilinear (Fig. 1).Bromothymol blue was found to be a more suitable indicator than phenolphthalein, which was used earlier,4 and its use 3 Volume of 0.1 N H2S0,/ml Fig. 1. Titration of beryllium, in the presence of tartrate and fluoride, with standard acid.BELL 125 resulted in better stoicheiometry. The over-all analytical relationship is that 1 mol of beryllium is equivalent to 1.5 mol of hydrogen ion. An excess of tartrate must be used to complex the beryllium and must be added before adjustment to pH 7.0 or to the visual end-point of the indicator. The addition of excess of fluoride to the basic beryllium tartrate complex, formed at this pH, is necessary to liberate completely hydroxide ion, which is then titrated against standard acid.Under these conditions empirical standardisation via beryllium is unnecessary. Experimental Owing to their toxicity, extreme care should be taken when using beryllium compounds, especially when finely divided powders. Caution: the standard code of practice for handling beryllium compounds should be strictly adhered t o Y Apparatus for the potentiometric pH determinations. continuous stirring was effected with a magnetic stirrer. A Pye, Model 79, pH meter with a glass - silver chloride combined electrode system was used Titrant was added from a 10-ml burette and Reagents Beryllium solutions. Standard solutions, prepared from beryllium flake ( >99-9 per cent., Koch-Light Ltd.) were used in establishing the experimental method.Solutions were made up in 1 M sulphuric acid. Potassium sodium tartrate solution, 0.5 M. This solution is stable only for 1-2 months at room temperature. Replace the solution when a fluffy white solid forms as a result of micro- biological activity. This solid has been shown by microscopic examination to consist of an association of a filamentous alga and a bacillus. The lifetime of the solution can be prolonged by storing it below room temperature. PotassiumJlzcoride solution, 1 M, Adjust the pH of this solution by the addition of sulphuric acid, such that when a 5-ml portion is diluted to about 80 ml, the pH of the resulting solution is 7.0. Prepare these solutions by accurate dilution of ampoules of concentrated volumetric solutions.Standard sodium hydroxide and sulphuric acid solutions, 0.01 and 0.1 N. Indicators. Prepare by use of the standard methods.' Diverse ions. Prepare stock solutions from analytical-reagent grade nitrates, chlorides or sulphates of various bivalent metal ions. Sodium salts were used to study the effect of anions. Methods (i) Visual titrimetric method Add 5 ml of the potassium sodium tartrate solution to an aliquot of one of the beryllium solutions, followed by four drops of bromothymol blue indicator solution. Make the solution alkaline (blue) with sodium hydroxide solution (about 0.1 N) and then neutralise it (green) by adding the appropriate standard sulphuric acid dropwise from a burette.Add 5 ml of potassium fluoride solution, stir, and, after 5 min, titrate the liberated hydroxide ion with the standard acid. For solutions containing 0.1-1.8 mg of beryllium, use 0.01 N sulphuric acid, and in the range 14-16 mg, use 0.1 N acid. Up to 9mg of beryllium, 5rnl each of potassium sodium tartrate and potassium fluoride solutions suffice. In the range 9-16 mg, use 10ml of each. (ii) Potentiometric method Add potassium sodium tartrate solution to the solution containing beryllium, making the volume up to 70-80 ml with water. Adjust the solution to pH 7.00 and then add potassium fluoride solution. After 5 min, slowly titrate the solution back to pH 7.00, using standard sulphuric acid solution. Use the same volumes of tartrate and fluoride solutions and acid concentrations as in the visual method.For solutions of pure beryllium sulphate (i-e., containing no added acid) it was found to be unnecessary to use the fluoride procedure. Add potassium sodium tartrate solution to126 Analyst, Vol. 100 the beryllium solution and then titrate the mixture to either pH 7.00 or to the visual end- point by using bromothymol blue indicator with standard alkali (0.1 N for 1-27 mg and 0.01 N for 0.1-1-5 mg of beryllium). BELL : THE TITRIMETRIC DETERMINATION OF BERYLLIUM Interferences The effect of several foreign elements on the determination at the 0.3 mg of beryllium level was investigated. The experimental procedure for eliminating or reducing the interferences prior to adjustment of the solution to pH 7.00, before addition of fluoride, is indicated in Table I.EDTA was used as a masking agent throughout this study. After the addition of tartrate to the solutions containing the metal ions, they were adjusted with alkali to the appropriate pH for complexing the diverse ions. A few drops of the indicator solution were added, followed by the dropwise addition of EDTA solution. The appropriate pH was main- tained by the simultaneous addition of alkali until complexation was complete, at which point the indicator changed colour. Then the solution was adjusted to pH 7.00, fluoride added, and the solution treated as in the standard method. Because the method is based on the significant increase in the pH of the solution that occurs on addition of fluoride, it was important to add only a very slight excess of EDTA to ensure complexation of the metal ions, otherwise buffering of the solution occurred.The use of a visual indicator to show that complexation was complete dictated that beryllium could only be determined by use of the potent iomet ric met hod. TABLE 1 REDUCTION OF INTERFERENCE EFFECTS OF VARIOUS BIVALENT METAL IONS AT THE 0.3 mg O F BERYLLIUM LEVEL Metal c u Mn c o Ni Cd Pb Ca Zn Rangelmg 1.6-9 1-2-7-6 0.03-6 0.006-0.6 1 1-300 P200* 2-30 0*3-100 pH for complexing 10.0 8-9 6-6-6.8 -9 6.6-6-8 -6 -1 1 11.0 Tempera- ture/"C 40 20 40 20 20 20 20 20 Indicator 13-iochrome black T, 3 drops Eriochrome black T, 3 drops Xylenol orange, 3 drops Murexide, 0.2 g Xylenol orange, 2 drops Xylenol orange, 3 drops lkiochrome black T, 3 drops Murexide, 0-2 g Colour change Red - blue Red - green Red - orange yellow Yellow - violet Red - yellow Red - yellow Red - violet Red - blue * For amounts of lead greater than 60 mg, i t is necessary to use volumes of liquid greater than 100 ml so as to prevent the formation of a white precipitate upon the addition of tartrate.With solutions containing copper(I1) ions at concentrations above about 9 mg of copper, the deep blue colour of the solution masked the colour change of the indicator. If most of the copper was removed as the sulphide, the excess of hydrogen sulphide boiled off and the remaining traces of copper complexed with EDTA, then beryllium could be determined accurately in a solution that initially contained 'beryllium and copper in a ratio of up to 1 : 1500. Results For the determination involving the use of the fluoride procedure the standard deviation at the 14mg of beryllium level was &0.051, while at the 0.3-mg level it was &0-0042 for the potentiometric method and &0.0054 for the visual indicator method.Application of the Student t-test showed that the results were not significantly different at the 95 per cent. confidence level, whether the acid was standardised in terms of known amounts of beryllium or the content was calculated from the analytical relationship that 1 mol of beryllium is equivalent to 1.5 mol of hydrogen ion. For solutions containing only beryllium sulphate, the metal content over the range 0.1-28 mg (Fig. 2) could be established without resorting to the fluoride procedure by direct titration of the beryllium tartrate complex with alkali.At the 0-3-mg level the standard deviations were &0*0027 for the potentiometric method and Ifi0.0036 for the visual indicator method, while at the 14-mg level they were &to4345 and &0.05, respectively.February , 1975 BY USING THE TARTRATE - FLUORIDE PROCEDURE 127 The effect of diverse ions on the determination of beryllium at the 0.3-mg level has been examined. This level was chosen as being within the range of the recommended procedure, requiring a sufficiently large titration volume and giving adequate precision to establish interference effects. The minimum amounts of cation that were found to be tolerable at the 0.3-mg level of beryllium are the lower values in the range column in Table I; the higher values indicate the maximum level of diverse species tolerable when the EDTA procedure was applied.Results were considered to be acceptable between &2x (standard deviation). Attempts to reduce or eliminate the interference effect of the metal ions were successful in all instances that were examined, except for magnesium and aluminium, for which the maximum permissible amounts were 1-1 and 0.05 mg, respectively. Volume of 0 . 1 ~ NaOH/ml Fig. 2. Titration of beryllium, in the presence of tartrate, with standard alkali. Chloride (greater than 2300 mg), bromide (greater than 3200 mg), iodide (greater than 3300 mg), nitrate (greater than 1000 mg) and sulphate (greater than 1000 mg) ions did not interfere in the determination but sulphide ion did, although no attempt was made to establish the minimum interference level as it could readily be removed by boiling the acidified solution for a few minutes.This method has been used for the determination of beryllium in a wide range of its organic, halide and hydride complexes. Some typical examples and results are given in Table 11. TABLE I1 DETERMINATION OF BERYLLIUM IN SOME COMPLEXES Beryllium, per cent. r [But OBeCl.THF], . . .. 4.70 (8) 4.75 EtBeClbipy . . . . .. 3.95 (9) 3.93 Complex Found (reference) Calculated [HBeNMeC,H,NMe,], . . . . 8.21 (10) 8.12 Discussion The tartrate - fluoride procedure for the determination of beryllium has been re-investigated and shown to be stoicheiometric, rapid and precise, and applicable over the range 0.1-16 mg of beryllium.The method allows the determination of beryllium in the presence of limited amounts of diverse cations, although the interference effect can be reduced with EDTA. For example, at the 0-3-mg level, beryllium can be determined in the presence of 12 times its mass of lead in the absence of EDTA and 600 times its mass in the presence of EDTA. This titrimetric method for the determination of beryllium is more accurate and has a wider range than the method involving sodium sulphosalicylate or salicylates, in which the128 BELL error in the determination of 1-5 mg is less than d15 per cent. and copper and aluminium in 80-fold excess interfere.ll The photometric titration of beryllium with sodium sulphosalicylate requires the addition of an excess of reagent and the excess to be back-titrated with standard beryllium solution.The range of this last method is 0.05-15 mg, with a standard deviation of *0.004 at the 3-mg level and &0.003 at the 0.8-mg level. There is thus little difference between the range and precision of this photometric method [in which the interference of many elements can be reduced by the addition of (1,2-cyclohexylenedinitrilo) tetraacetic acid or EDTA12] and the method proposed in this paper. 1. 2. 3. 4. 6. 6. 7. 8. 9. 10. 11. 12. References Smythe, L. E., and Whittem, R. N., Analyst, 1961, 86, 83, and references cited therein. McClure, J. H.. and Banks, C. V., Rep. Congr. Atom. Energy Commn., U.S., AECU812, 1950. Booth, E., in Wilson, C. L., and Wilson, D. W., Editors, “Comprehensive Analytical Chemistry,” Volume IC, Elsevier Publishing Company, Amsterdam, London and New York, 1962, p. 62. Zolotukhin, V. K., Trudy Kom. Analit. Khim., 1954, 5, 224. Everest, D. A., “The Chemistry of Beryllium,” Elsevier Publishing Company, Amsterdam, London and New York, 1964. Tepper, L. B., Hardy, H. L., and Chamberlin, R. I:., “Toxicity of Beryllium Compounds,’’ Elsevier Publishing Company, Amsterdam, London and New York, 1961. Vogel, A. I., “Quantitative Inorganic Analysis,” Third Edition, Longmans, Green and Co. Ltd., London, 1968. Anderson, R. A., Bell, N. A., and Coates, G. E., J . Chem. Soc. Dalton Trans., 1972, 677. Bell, N. A., J. Organomctal. Chem., 1988, 13, 613. Bell, N. A., and Coates, G. E., J . Chem. SOC. A , 1968, 823. Kalinichenko, L. P., and Kalinichenko, I. I., Russ. J . Analyt. Chem., 1962, 17, 828. Florence, T. M., and Farrar, Y. J., Analyt. Chem., 1963, 35, 712. Received March 28th, 1973 Amended September 2nd, 1974 Accepted September loth, 1974

ISSN:0003-2654    

DOI:10.1039/AN9750000124

出版商:RSC    

年代:1975

数据来源: RSC

摘要:

Analyst, February, 1975, Vol. 100, p p . 129-135 129 A Method for the Assessment under Standard Conditions of the Output of Dichlorvos Slow-release Units Used for Insect Control S. G, Heuser and K. A. Scudamore Ministry of Agriculture, Fisheries and Food, Pest Infestation Control Laboratory, London Road, Slough, Berkshire A test method is described for the measurement, under standard conditions, of the amount of dichlorvos (00-dimethyl 2,2-dichlorovinyl phosphate) vapour emitted from insecticide slow-release units. Specimen results, ob- tained under these conditions, are given for the outputs of several types of unit during the initial 14-d period when output is greatest, with corr- esponding values for the concentration of dichlorvos in the air in a 28-m3 room where constant temperature and humidity are maintained.The relationship between unit output and the concentration developed in the air under various environmental conditions is discussed and the application of the method in the comparative assessment of the potential safety in use of different types of unit is proposed. An increasing number of types of unit, designed for insect control by the continuous slow emission of dichlorvos (00-dimethyl 2,2-dichlorovinyl phosphate) vapour into the surrounding atmosphere, is being manufactured for marketing in the United Kingdom and elsewhere. Their use is widespread in the home, in public places and in commercial premises. The insecticide, a liquid at room temperature, may be incorporated as a solution in a homogeneous or granular plastic base such as poly(viny1 chloride), polyethylene or polyester resin with various other additives.Alternatively, the element may comprise an inert matrix, for example, of fibre-glass or cellulose fibre, in which is incorporated a resin containing the insecticide, or, the dichlorvos may be absorbed in the porous structure of a rigid material such as a ceramic. One or more stabilisers, acting as antioxidants or inhibitors of hydrolysis, can be incorporated in order to prolong the shelf or active life of the unit. The element is usually surrounded by a protective casing to prevent handling and this casing is sometimes designed so as to allow adjustment of the amount of surface area of the element exposed to the air, thereby controlling its vapour output. Other factors that affect the rate of vaporisation of dichlorvos from such dispensers are the composition of the element base, the amount of toxicant remaining, the ambient tem- perature, the rate of air movement in the vicinity of the unit and in some circumstances the concentration of the vapour surrounding it.In addition, the vapour concentration produced in a given space by a particular rate of output of dichlorvos is governed by the rate of ventila- tion, the sorptive nature and temperature of the surface exposed to the vapour and the rate of breakdown of dichlorvos in air, which is itself dependent on the ambient temperature and humidity. For the customer, two main considerations attend the marketing of these devices, effective- ness and safety in use, and in view of their widespread employment, the second of these criteria must also apply to the general public.While measurement of the output of dichlorvos from a slow-release unit over a limited period of time may give an indication of its effectiveness and of its life expectancy for the control af pests, the primary function of the test described in this paper is to determine whether unaccqtabk concentrations of dichlorvos in air are likely to result when units are used in accordance with the manufacturer’s instructions. Scope and Limitations of Testing With so many variables it becomes difficult to define a “standad” room and conditions for its operation in which objective measurements of concentration can be made for regulatory 8 Crown Copyright Reserved.130 Analyst, VoZ.100 use, although this has been attempted.l A given room may, however, be of value for com- parative tests between units. Another and perhaps more realistic approach is to assess the accumulated available data on the concentrations of dichlorvos in air produced by certain types of unit under a variety of practical condition^,^^^ for example, in home kitchens, living rooms and bedrooms, restaurants and offices and, where it is agreed that these concentrations are acceptable, to relate them to the measured output of units subjected to a standard test in which collection of the emitted vapour is carried out under controlled conditions. It is implicit that under the conditions of such a test, the rate of output of toxicant must be close to that achieved when the unit is freely exposed in a room at the same temperature, i e ., that the test conditions should approximate to normal conditions of use. This provision must hold for each type of unit tested. The test described below has been designed to meet these criteria. HEUSER AND SCUDAMORE: ASSESSMENT OF THE OUTPUT Test Method Apparatus The apparatus used for entrainment of the dichlorvos vapour emitted from the slow- release unit under test is shown in diagrammatic: form in Fig. 1. The structure of the glass components used to ensure standard surface exposure to the vapour before its absorption is illustrated in Fig. 2. PTFE gaskets are used between those parts of the apparatus exposed to the dichlorvos vapour where retention of the compound would lead to errors in measure- ment.Bubblers are butt-jointed to hose-connectors by means of short lengths of silicone- rubber tubing. Fig. 1. Flow diagram of apparatus for measurement of dichlorvos released from dispensers under controlled conditions: A, main flow meter (0-60 1 min-') ; B, test chamber; C, main flow control valve; D, absorption bubblers; E, subsidiary flow meter (0-0-6 1 min-l); F, subsidiary flow control valve; G, pump. The cylindrical glass chamber (B) (225 mm in internal diameter and 400 mm long) fitted with de-mountable conical glass ends, houses the slow-release unit under test. The unit is suspended centrally from a stainless-steel insert clamped between two gaskets at the upper neck of the chamber. The whole apparatus is maintained at a temperature of 25 -+ 0.2 "C.Air at constant temperature and relative humidity is drawn downwards over the slow- release unit by means of a vacuum or other suita.ble type of pump (G). The main air flow over the unit under test is set by the diaphragm valve (C) and measured by the flow meter (A) on the inlet side. During vapour collection, a proportion of the air, which contains dichlorvos vapour emitted from the unit, is diverted through two absorption bubblers (D), each containing 50ml of de-ionised water, for analysis. About 95 per cent. of the dichlorvos is collected in the first bubbler. The rate of flow through the bubblers, recorded on a second flow meter (E), is controlled by a subsidiary flow control valve (F). When vapour is not being collected for analysis, a by-pass tube is fitted in place of the bubblers so that valve (F) requires only fine adjustment upon connection of a further set of bubblers.February, 1975 OF DICWLORVOS SLOW-RELEASE UNITS 131 From inlet w flow meter Insert Hose connector PHC 1/.75 I I \PTFE gasket TR9 Pipe section PS9/400 omrr===pnolC9 + TR9 Diaphragm C1 + CGNl valve DVS 1 (Neoprene gasket) \ / \ --C1 +TR1 H PB 90/1 PH C - To 11.75 To absorption bubblers, v 1 subsidiary flow meter, PHC 07/.4 and valve F (see flow diagram) Fig.2. Standard glass components for dichlorvos collection system (not to scale). Couplings C07, Cl and C9 comprise sets of flanges, inserts and bolts and require appropriate PTFE or Neoprene gaskets. Glassware and Jittings Quantity 1 2 1 2 2 2 1 2 6 2 2 6 2 2 1 Ancillary equipment 1 1 1 1 2 1 Description Part No.* Pipe section PS9/400 Pipe reducers PR9/1 90' bend PB9O/l Unequal T-pieces PTU 1 /07 Hose connectors PHCl /.76 Hose connectors PHCO'II .4 Diaphragm valve DVS 1 Couplings c 9 Couplings c1 Couplings C07 PTFE gaskets TR9 PTFE gaskets TRl PTFE gaskets TR07 Neoprene gaskets CGNl Stainless-steel insert, 38 mm in diameter? Pump with displacement of air up to 50 1 min-1, continuous rating Flow control valve 100-600 ml min-' Flow meter 0-60 1 min-l of air Flow meter 0-600 ml min-l of air Absorption bubblers, 100-ml capacity, sintered glass, porosity 0 By-pass tube, 7 mm 0.d. * All part numbers refer to QVF pipeline fittings, obtainable from James A. Jobling and Co. Ltd. t Not standard. Requires fabrication-see Fig. 2. Procedure When the initial mass of the slow-release unit under test has been determined, it is placed in position in the cylindrical chamber.The upper conical section is bolted down and then132 AnaZyst, V d . 100 air, free from dichlorvos vapour and pre-conditioned to a temperature of 25 & 0.2 "C and to a relative humidity of 60 & 5 per cent., is passed over the unit continuously at 30 & 2 1 min-1. (N.B. It is convenient to maintain at the required conditions the room in which the apparatus is located. Air leaving the apparatus must be vented to the atmosphere at a point remote from the inlet, preferably outside the building.) The rate of flow through the subsidiary arm, with the by-pass tube in position, is set at approximately 200 ml min-l by means of the flow control valve F.Twenty-four hours after the main air flow is commenced, the first set of bubblers is connected in place of the by-pass tube. The flow-rate is adjusted as nearly as possible to 200 ml min-l and the bubblers are left in position for a total of 2 h. Different sets of bubblers are connected for 2-h periods at 24-h intervals over a total period of four consecutive days. At the end of this time the unit is removed from the apparatus and re-weighed. The contents of the bubblers, stored at 1-2 "C, are analysed within 24 h. Either a cholin- esterase-inhibition technique (which is, however, not specific for dichlorvos) or gas-chromato- graphic analysis can be employed. The recovery factor for the apparatus is calculated after determining the proportion collected in the bubblers when a small weighed amount of pure dichlorvos deposited on a glass slide is held in the flow chamber until evaporation is complete.After each unit test or recovery test the inner surfaces of the main chamber are wiped thoroughly with a damp cloth and allowed to dry completely in a current of air before further testing is undertaken. HEUSER AND SCUDAMORE: ASSESSMENT OF THE OUTPUT Presentation of Data From the amounts of dichlorvos collected in tbe bubblers, the total output of a slow-release unit in each 24-h period can be calculated, taking into account the relative flow-rates and the recovery factor for the apparatus. These outputs should be tabulated for the 4 d of the test, together with the relevant flow-rates, the temperature and relative humidity of the air input and the mass of the unit at the beginning and end of the test.Other relevant data would include the composition of the element of the slow-release unit and the minimum volume of air space for which it is designed. It is suggested that the test be carried out on three unused examples of slow-release units. Development and Validation of Test Procedure A fresh unit was placed in the main chamber (B). Air, supplied from the room, maintained at constant temperature and humidity, in which the apparatus stood, was drawn continuously over the unit. After allowing an initial period of 24 h for the attainment of moisture equilibrium a proportion, set by means of the main and subsidiary flow meters, of the effluent air containing dichlorvos was passed through aqueous absorption bubblers with subsequent analysis of the solution by a cholinesterase-inhibition m e t h ~ d .~ A suitable flow-rate for the bubbler system, using 50 ml of water in each scrubber and porosity 0 sintered glass frits, was found to be 200mlmin-l. Initially, tests were made with 24-h collection periods, but it was subsequently found that 2-h collection periods in each 24 h of continuous flow gave results that allowed calculation of the output over 24 h with little error (Table I). TABLE I CALCULATION OF DAILY OUTPUT OF DICHLORVOS OF A SLOW-RELEASE UNIT, BASED ON SHORT AND LONG SAMPLING PERIODS Sampling period (successive) /h 2 2 20 2 2 20 2 2 Room temperaturel'c 26.7 25.6 26.5 26.6 26.6 25.6 25.5 26.4 Amount of dichlorvos Output calculated collected/mg for 24 h/mg 13.1 167 13.6 162 131-4 158 13.3 169 13-3 159 124.2 149 12-6 161 12.7 162February, 1975 O F DICHLORVOS SLOW-RELEASE UNITS 133 Signi$cance of $ow-rate To determine the required rate of main air flow in the apparatus an identical slow-release unit (of the same batch) was suspended in an unventilated room (in which the air was stirred with a fan) of 28-m3 volume (3.35 m x 3.05 m x 2-75 m high) that had gloss-painted walls and an eggshell finish, emulsion-painted ceiling.This room was maintained at the same temperature and humidity as the apparatus and the daily mass loss of the unit was recorded (Table 11). It is unsatisfactory to attempt to estimate the output of dichlorvos of units by loss in mass alone as many units contain volatile compounds other than the toxicant and some types of unit gain or lose moisture in response to changes in the relative humidity of the surrounding air, especially during the initial equilibration period (see Table 11).How- ever, it can be assumed that for identical units, under the same conditions of temperature and relative humidity, a reasonably constant proportion of the loss in mass over a limited period will be due to vaporisation of dichlorvos. Hence, a pair of identical units losing the same amount in a given period under these conditions can be said to have approximately the same rate of dichlorvos emission. If the dichlorvos emitted from one of these units is collected and analysed in the apparatus, then this analysis provides a close estimate of the output of the other unit, which is suspended in the room, and so it is possible to relate this output to the concentration of dichlorvos vapour in the room.The rate of air flow in the apparatus used in the tests described was adjusted until the mass loss per unit time of pairs of identical units corresponded as nearly as possible. Day 1 2-4 7-9 10-14 TABLE I1 LOSS I N MASS, OUTPUT OF DICHLORVOS AND TEST-ROOM CONCENTRATIONS FOR DIFFERENT UNIT TYPES Unit and element type 1 2 3 4 5 6 f A -t Impreg- Impreg- Impreg- Impreg- nated nated nated nated Mean 24-h results Plastic Plastic fibre-glass ceramic fibre pad fibre pad Mass loss, apparatuslg . . 0.40 0.19 0.60 9.15 -0.03* -0.83+ Mass loss, room/g . . . . 0.23 0.08 0.97 8.28 -0.25* -1.10'' Dichlorvos collected/g .. 0.32 0.15 0.23 0.39 0.1 1 0.07 Room concentration/pg 1-1 0.39 0.17 0.50 0.48 0-14 0.07 Mass loss, apparatusfg . . 0.43 0.22 0.49 1.48 0-25 0.36 Mass loss, room/g . . . . 0-32 0.19 0.65 1-23 0-2 1 0.14 Dichlorvos collected/g . . 0.35 0.16 0.29 0.62 0.12 0.08 Room concentration/pg 1-1 0-43 0.23 0.48 0.67 0.19 0.07 Mass loss, apparatuslg . . 0.36 0.22 0.35 0.83 0.22 0.26 Mass loss, room/g . . . . 0.28 0.33 0.38 0.56 0-18 0-17 Dichlorvos collected/g . . 0-27 0.15 0.30 0.49 0.11 0-06 Room concentration/pg 1-1 0.43 0.31 0.34 0.89 0-20 0.07 Mass loss, apparatus/g . . 0.31 0.25 0.2 8 0.62 0.20 0.18 Mass loss, room/g . . . . 0.26 0.37 0.30 0.48 .0.15 0.14 Dichlorvos collected/g . . 0.26 0.18 0.29 0.42 0.10 0.06 Room concentration/pg 1-1 0.45 0.30 0.33 1.06 0.17 0.06 * These results represent mass gains.For a variety of types of unit this flow-rate was in the range 30 6 1 min-l (linear velocity approximately 0.75 m min-l). Neither mass loss nor measured output of dichlorvos altered materially when units were moved to different axial positions in the flow chamber, even when units had slotted covers (in a fully open position). After calculation at the design stage of the desired range, the flow-rate required for this test was determined empirically. However, for a median output of 300mg of dichlorvos per 24 h at a flow-rate of 30 1 min-l (see Table 11), the average vapour concentration in the entraining air would be approximately 7 pg l-l, which is about 50 per cent. of the level at which significant inhibition of output of units begins to occur in static small-chamber tests. The lower output obtained when the volume flow-rate is reduced, compared with mass loss in a room, can be explained on the above basis.The minimum total air flow requirement134 HEUSER AND SCUDAMORE: ASSESSMENT OF THE OUTPUT Ana&St, Vd. 100 also dictates the diameter of chamber necessary to avoid an excessive linear air velocity. Both linear and total air flow affect output, the latter being of considerably more importance in a small chamber where the saturation level is significant. During the course of develop- ment, testing and submission for comment to manufacturers and Government safety com- mittees of the method described here, a similar rapid test has been devised by Lynchs and used for batch control and other comparison purposes.However, Lynch's apparatus, in which a flow-rate of 9.5 lmin-1 is employed, is designed for use within the output range 24-192 mg of dichlorvos per 24 h at 25 "C, which is considerably below the output found to be typical of some types of unit (when fresh) when they are placed in a room (Table 11). Discussion of Results and Application of Data A number of different types of slow-release unit currently marketed in the United Kingdom have been tested in the apparatus described here and their measured outputs over periods of up to 14 d are recorded in Table 11, together with the corresponding mass loss data. For the purposes of comparison of different types of slow-release unit, if a positive correlation can be shown, irrespective of the type of unit, between the rate of output measured under standard conditions and the average vapour concentration developed in a given room when the unit is emitting a comparable amount of dichlorvos, it is reasonable to postulate that maximum concentrations likely to be developed under the variety of conditions experienced in practice will bear a similar relationship to the measured output.This relationship can provide a basis for decisions on acceptability without the need for repetition of large-scale sampling operations in respect of each new type of unit that it is proposed to market. The relationship between the average daily output of dichlorvos as measured in the appara- tus over a period of 14 d and the average concentrations developed under controlled conditions in the 28-m3 room by units that lose approximately corresponding amounts over the same period (Table 11) was established as rectilinear (Fig.3). The measured output can therefore be used as an indication of the relative potential of each type of unit to produce a level of concentration of dichlorvos and these levels can be compared under any particular set of conditions. It was established that the maximum rate of output from all but one of the units tested (Type 3) was reached within 4 d (Fig. 4). The output of the remaining unit declined after 6 d. It is suggested, therefore, that standard measurements for evaluation of acceptability should be carried out over a 4-d period after the initial 24 h for conditioning. Y- 0.1- v) 2 Average concentration/pg I-' Fig.3. Relationship between the concentra- tions of dichlorvos developed and the average daily output from each unit. 5 c 6 * I I I I It was found that of those tested only one type of unit (Type 4, Table 11) consistently exceeded an output of 0.3-0.4g of dichlorvos per 24 h, approximately the level reached at 25 "C with units of the type whose perforrnance under a variety of field conditions has been most widely recorded. Under the experiment a1 conditions, in which each unit was suspended in an unventilated 28-mS room at 25 "C and 60 per cent. relative humidity, the Type 4 unit was also the onlyFebruary, 1975 OF DICHLORVOS SLOW-RELEASE UNITS 136 one that produced (between day 10 and day 14) a concentration level above the threshold limit of 1.0 pg of dichlorvos per litre adopted in 1964 by the American Conference of Govern- mental Industrial Hygienists6 It is of interest to note that with this type of unit the room concentration remained at a high level although the measured dichlorvos output and mass loss had begun to decline after day 4.Also, the extreme disparity, with both Types 4 and 6, between the mass loss of the units and their measured output of dichlorvos, in the first few days of exposure after unpacking, should be noted. Conclusions The experimental measurements and results reported support the use of a test of the nature described and provide evidence that when the specified apparatus is employed as directed, the results obtained can be used to predict comparative concentration levels that are likely to be achieved in a given set of circumstances, when data already available are taken into consideration. It is concluded that mass loss can be used only as a guide to the output of dichlorvos and that mass measurements made in the first few days of exposure may give highly anomalous results with some types of unit. It should be noted that manufacturers stipulate various room volumes in which it is recommended their products be used and this factor may be taken into account in assessing comparative concentrations of dichlorvos in air that are likely to be achieved with a given output ; however, it cannot be assumed that these recommendations will always be observed. For this reason, too, it is desirable to assess the maximum potential output of units that have variable orifices. References 1. 2. 3. 4. 6. 6. Batth, S. S., Singh, J., and Villeneuve, D. C . , J . Econ. Ent., 1973, 66, 146. Elgar, K. L., and Steer, B. D., Pestic. Sci., 1972, 3, 691. Collins, R. D., and DeVries, D. M., Bull. Envir. Contam. Toxicol., 1973, 9, 227. Michel, H. O., J . Lab. Clin. Mad., 1949, 34, 1664. Lynch, D., Mfg Chem., 1974, 45, 39. Ashe, H. B., Baier, E. J., Coleman, A. L., Elkins, H. B., Grabois, B., Hayes, W. J., jun., Jacobsen, K., Macefarland, H. N., Mastromatteo, E., Reindollar, W. F., Scovill, R. G., Smith, R. G., Zavon, M. R., and Stokinger, H. E., A r c h Envir. Hlth, 1964, 9, 645. Received July 31st, 1974 Accepted September 2&k, 1974

ISSN:0003-2654    

DOI:10.1039/AN9750000129

出版商:RSC    

年代:1975

数据来源: RSC

摘要:

136 Analyst, February, 1975, Vol. 100, pp. 136-141 Recommended Methods for the Evaluation of Drugs PREPARED BY THE JOINT COMMITTEE OF: THE PHARMACEUTICAL SOCIETY AND THE SOCIETY FOR ANALYTICAL CHEMISTRY ON RECOMMENDED METHODS FOR THE EVALUATION OF DRUGS The Assay of Ephedrine In September, 1969, the Joint Committee of the Pharmaceutical Society of Great Britain and the Society for Analytical Chemistry appointed a working panel to recommend standardised methods of assay of sympathomimetic drugs and their formulations, and it was expected that gas - liquid chromatography would be the method of choice. The constitution of the Panel was: Mr. J. C. Deavin (Chairman), Mr. J. S. Foster, Dr. M. Mitchard, Mr. D. H. Mitchell, Mr. R. Sinar (resigned June, 1971), Mr. R. N. Thornhill, Mr.D. A. Wheeler and Mr. E. Fuller (appointed August, 1970), with Mr. P. W. Shallis as Secretary. The terms of reference of the Panel were “To investigate the assay of sympathomimetic amines with particular reference to gas - liquid chromatographic methods.” Introduction Members agreed that the Panel should investigate a method for the assay of ephedrine initially, in view of its wide usage, then consider ephedrine formulations and finally apply the method to other sympathomimetic mines. The obFjective of the Panel was to produce a method of assay which would (i) be suitable for inclusion in monographs of formulated products containing ephedrine in future editions of the Bnitish Pharmacopoeia and British l?harmaceutical Codex and (ii) be adaptable with a miuimum of modification for the determination of the sympathomimetic amine content of other formalations.The alkaloidal base ephedrine is extremely volatile and is not suitable for gravimetric determination. This volatility is a property that is used for the assay of galenicals containing the alkaloid or its salts and the Analytical Methods Committee of the Society for Analytical Chemistry1 has recommended a distillation procedure for the determination of ephedrine in nasal sprays. This method, however, is tedious and time consuming. According to Welsh,2 ephedrine can be acetylated quantitatively in aqueous solution to yield a neutral N-acetyl derivative, which can be extracted with chloroform. Hydrogen sulphite interferes with the acetylation and must first be removed by addition of a slight excess of iodine in acidic solution, followed by decolorisation with thiosulphate.Sanchez3 determined ephedrine by its reaction with alkaline iodine solution at 50 “C to form iodoform and titration of the excess of iodine in acid solution. Application of this method to standard solutions of ephedrine hydrochloride has given recoveries within &3 per cent. of the theoretical values. However, when attempting to apply this method to the deter- mination of ephedrine hydrochloride in cough imixtures it has proved of no value because gross interference from other constituents necessitates preliminary separation of ephedrine, usually by steam distillation, and in such a distillate ephedrine can be determined more rapidly and precisely by acidimetric titration. Horkk and GaSperik4 used a method for the determination of ephedrine based on the liberation, by alkali hydrolysis, of methylamine, which can be determined on the semi-micro scale in the Kjeldahl apparatus and these workers claimed good results when this method was used for the determination of ephedrine hydrochloride in pharmaceutical injections and tablets.The specificity of the spectrophotometric determination of ephedrine and other phenylalkanol- amine drugs as benzaldehydes extracted after periodate oxidation has been demonstrated.5 It is shown that the compounds must have the general structure Ar-CHOH-CH(NHR)-R’, that Ar cannot be an o-dihydroxyphenyl group (catecholamines do not interfere), that the amine function must be basic and sterically unhindered and that there is no mutual interference between phenolic compounds and benzaldehyde-forming drugs.The periodate oxidationTHE ASSAY OF EPHEDRINE 137 method will not distinguish between compounds such as ephedrine and phenylpropanolamine, both of which yield benzaldehyde, or phenylephrine and metaraminol, both of which give 3-hydroxybenzaldehyde. It will not discriminate stereoisomers such as ephedrine (erythro configuration) and pseudoephedrine (threo configuration). It was decided, in view of the limited specificity of existing methods, to investigate a gas - liquid chromatographic procedure for the assay of ephedrine and related sympatho- mimetic amines; such a method would also have the advantage of determining likely im- purities, although there was no guarantee that the method would successfully separate ephedrine from related sympathomimetic amines.Experimental The Panel began its work by investigating a modification of the method proposed by Beckett and Wilkinson.6 All members followed the same procedure for the extraction of the liberated ephedrine base, but some variations in gas-chromatographic conditions were necessary owing to the different types of gas chromatograph used in this work. The instru- ments used by the members were: Varian Aerograph 204B with stainless-steel column (injection not on-column) Gas-Chrom S.6 with stainless-steel column (injection not on-column) Perkin-Elmer F11 with glass column (injection on-column) Pye 104, Model 24, with glass column (injection on-column) F & M 5750 with stainless-steel column (injection on to stainless-steel insert liner) The packing used in the column was 80-100-mesh, acid-washed, silanised Chromosorb G impregnated with 2 per cent.of Carbowax 6000 and 5 per cent. of potassium hydroxide. Phendimetrazine bitartrate was used as internal standard; the phendimetrazine base has a retention time of 3 min compared with 5 min for ephedrine base under the instrumental conditions used in this work. Various factors affecting the extraction of the liberated base and the gas chromatography were investigated and improvements in the method were incorporated during the work. Some tailing of the ephedrine peak occurred throughout the investigations and attempts to improve the peak symmetry did not meet with any real success.In addition to investigating the assay of ephedrine hydrochloride, Ephedrine Hydrochloride Tablets BP, Ephedrine Elixir BPC and Ephedrine Nasal Drops BPC, the Panel also carried out collaborative tests on pseudoephedrine, phenylpropanolamine, methoxamine, orciprenaline, phenylephrine and methylephedrine. The possibility of assessing the accuracy of the gas chromatography step without the complicating effect of the extraction of the free base was considered. However, problems associated with the distribution of free ephedrine base for collaborative testing proved to be insurmountable. An examination by mass spectrometry and infrared analysis of the material representing the ephedrine peak confirmed that ephedrine base was eluted intact. Results and Discussion For the first test carried out two solutions of pure ephedrine hydrochloride were distributed to all members of the Panel, who, after extracting the free base, carried out five chromato- graphic runs on each extract, volumes of 2.5 and 5 pl being injected.Peak sizes were assessed by height and by area, measured by different means, and the results were reported as ratios of the value of the peak size for the sample to the value of the peak size for the internal standard. Results showed good agreement within laboratories, but considerable differences between laboratories were found. This was shown, in a further study, to be due to the need to specify more precisely the conditions for the extraction of the free base. Subse- quently, two solutions, each containing about 0.5 g of ephedrine hydrochloride and 0.5 g of phendimetrazine bitartrate, and a sample of Ephedrine Nasal Drops BPC were sent to all collaborators.The free base was extracted from each sample and five chromatographic runs were carried out on each extract, an injection of 1 pl being used. Results were again recorded as ratios of the value of the peak size for the sample to the value of the peak size for the internal standard, measurements on this occasion being made of peak height, retention distance and area. The area was assessed by cutting out the peaks from the chart paper and weighing and also by electronic integration. From the results it was concluded that the138 THE ASSAY OF EPHEDRINE Analyst, Vol. 100 method of assessing peak area by weighing was nlot satisfactory and that the result calculated from the peak height only was as satisfactory as the result derived from the product of peak height and retention distance.Some tailing of the ephedrine peak in this test was noted by some members. One member also carried out the work on two different chromatographs and obtained different ratio values. In view of this finding it was considered likely that the differences in ratio values between laboratories could be due to differences in the instruments used. Collaborative tests were carried out on samples of ephedrine hydrochloride, Ephedrine Hydrochloride Tablets BP, Ephedrine Elixir BPC, Ephedrine Nasal Drops BPC, pseudo- ephedrine hydrochloride, phenylpropanolamine hydrochloride, met hylephedrine hydrochloride and methoxamine hydrochloride.It was found necessary to alter the chromatographic conditions for some of these amines in order to achieve complete resolution. It was not possible, however, to resolve ephedrine and pseudoephedrine as they were eluted together from the column under all conditions. Preliminary studies indicate, however, that the method recommended in the Appendix is suitable for the determination of pseudoephedrine in the absence of ephedrine. Results obtained by the method recommended in the Appendix for the assay of ephedrine hydrochloride, Ephedrine Hydrochloride Tablets BP and Ephedrine Nasal Drops BPC are given in Table I. TABLE I EPHEDRINE NASAL DROPS BPC BY THE RECOMMENDED METHOD ASSAY OF EPHEDRINE HYDROCHLORIDE TABLETS BP AND Labora- Sample* tory 1 A B C D 2 A B Peak heights/mm & Phen.t 110 112 123 107 112 176 172 210 190 160 194 20 1 194.6 228 203.5 200.5 207 206 191 210 194-5 207 110 102.5 131 100 194 207 208 164.6 186 192 (W) 94.5 96.5 Ephedrine 107 110 125 113 102 111 177 172 209.5 191 164.5 140 161 141.5 178.5 165.0 159.0 165 165 151.6 167.5 156 166 115 103 139 106 (XI 90.5 199.5 217 222.5 165 195 194 Ratio (XlW 0.973 0-982 1.02 1.06 1-08 0.991 1.006 1.000 0.998 1-005 1.028 0.722 0.752 0-728 0.783 0-762 0.769 0.797 0.801 0.793 0-798 0.797 0.802 1-05 1.01 1-06 1.06 0.94 1-028 1.048 1.070 1.005 1.046 1.010 Ephedrine content 30.6 mg tablet 31.3 mg tablet 30.6 mg ta,blet Relative peak areas Phen. t EDhedrine - (Y) 110 109 123 107 94 1332 2115 2001 3199 31 14 2825 109 103 130 101 97 2529 2880 2967 2978 3229 3167 I L (2) 148 149 177 156 142 1973 3100 3039 5046 4596 4273 138 143 195 150 140 3698 4532 4688 42 62 4978 4624 Ratio Ephedrine (Z/Y) content 1.35 1-37 1.44 1.46 1.51 1.479 1.465 1.528 1.677 1.476 1.513 1-26 1-39 1.50 1-49 1.44 1.462 1.574 1.680 1.431 1.542 1.465 29.8 mg tablet 30.6 mg tablet 29.6 mg tabletFebruary , 1975 Labora- Sample* tory 2 C D 3 A B C D Peak heightslmm & THE ASSAY OF EPHEDRINE TABLE I-continued Phen.t 216 211 208.5 238 246 231 216 212.5 217 216 224.5 212 110 129.5 81 99 93.5 116 126.5 135 172 180 196 222.5 206 231.5 206 - 211.5 204 212.5 213 191.5 193.5 219 212 (W) Ephedrine 162 162 160 196 205.5 188 165 163.5 167.5 167 174 165 108 133 78 106 94 121 130 139.5 191 202.5 2 18-5 17.5 (XI 155 180 152.5 160 158 167-5 170 151 151 172 168 Ratio (XlW) 0.764 0.768 0.767 0.820 0.837 0.814 0.767 0.709 0.772 0.773 0.775 0.778 0-982 1.03 0.963 1.07 1-01 1-043 1.028 1-033 1.110 1.126 1-1 15 0.771 0.773 0.777 0.741 0.756 0.775 0-788 0.798 0.789 0.780 0.785 0.792 Relative peak areas Ephedrine Phen.t Ephedrine - content (Y) (2) 30.4 mg tablet 32.7 mg 29.1 mg Per tablet 29.4 mg Per tablet 109 148 I 7 188 1 mlv 98 149 0.494% 'i; 111 .I 94 134 0.604% ::ii iii; mlv 1493 2257 2162 3495 i mlv 2241 3696 0.545% 2319 3740 Ratio ( Z l Y 1.36 1.44 1.36 1.52 1-63 1-525 1-483 1-512 1.613 1.617 1.649 139 Ephedrine content * 1. 2. 3. Standard solution containing 0.5 g of ephedrine hydrochloride and 0.5 g of phendi- Ephedrine Hydrochloride Tablets BP (30 mg). Ephedrine Nasal Drops BPC (0.5 per cent.m/V). metrazine bitartrate in 200 ml of distilled water. t Phendimetrazine bitartrate, internal standard. It had been hoped initially to obtain a precision of *1.5 per cent. in the gas-chromato- graphic work, although this expectation was probably optimistic. The minimum require- ments of the British Pharmacopoeia for the validity of chromatograms, in particular the requirements relating to peak symmetry and the number of theoretical plates, were not always attained. In general, coefficients of variation within laboratories were not greater than 3 per cent. and in a collaborative test designed to establish linearity of response the calibration line produced by two members deviated significantly from the origin. The possi- bility of derivative formation was considered, but members felt that this would add another source of error and would not in any event be necessary if symmetrical peaks could be obtained.Despite the variety of different instruments used by the collaborating laboratories, agreement between laboratories was considered to be satisfactory. Conclusions The procedure recommended in the Appendix is adequate for the determination of ephedrine Measurement of relative peak areas by electronic in certain pharmaceutical preparations.140 THE ASSAY OF EPHEDRINE Analyst, Vol. 100 integration ensures the best results. When the peak height value is used, any tailing of the ephedrine peak will result in variation in peak haeight ratios. Assessment from the product of peak height and retention distance is also considered to be satisfactory but suffers from the same disadvantage as the measurement of peak height alone.APPENDIX Recommended Procedure for the Determination of Ephedrine in Certain Pharmaceutical Preparations Reagents Diethyl ether. Freshly distilled. Sodium hydroxide solution, 20 per cent. m/V. Sodium sulphate, anhydrous. Sodium chloride. Dichloromet hane. Sulphuric Acid, Dilute, BP. Chloroform BP. Phendimetrazine bitartrate solution, 1 per cent, m/V. Ephedrine Hydrochloride BP. For use as a standard. Preliminary Treatment of Official Preparations Ephedrine Hydrochloride Tablets BP Weigh and powder 20 tablets. Transfer an accurately weighed amount of the powder, equivalent to about 0.5 g of ephedrine hydrochloride, to a 200-ml calibrated flask, add 100 ml of water and shake for 5 min. Dilute to volume with water.Ephedrine Elixir BPC [ephedrine hydrochloride (0.3 per cent. m/V) in syrup-based formulation] To about 61.5 g (50 ml) of the sample, accurat:ely weighed, add 20 ml of water and 5 g of sodium chloride, and make slightly alkaline to litmus paper with sodium hydroxide solution. Add a further 06ml of sodium hydroxide solution and extract with six successive 20-ml portions of dichloromethane. Combine the dichloromethane extracts and extract with two 5-ml portions of dilute sulphuric acid and then four successive 5-ml portions of water. Wash the combined acid and aqueous extracts with 3 ml of chloroform, and discard the chloroform washings. Transfer the aqueous solution to a 50-ml calibrated flask with 5 ml of water, and dilute to volume with water. Ephedrine Nasal Drops BPC (ephedrine hydrochloride, 0.5 per cent.m/V). Preparation of standard solution and dilute the solution to 200 ml in a calibrated flask. Place 50 ml of the sample in a 100-ml calibraked flask and dilute to volume with water. Weigh accurately 0-5 &- 0.01 g of standard ephedrine hydrochloride, dissolve it in water Liberation and extraction of the free base Pipette 20.0 ml of the prepared solution (standard or sample) into a separating funnel and add 5 d of phendimetrazine bitartrate solution and 50 ml of 20 per cent. sodium hydroxide solution. Extract the liberated ephedrine bases with five successive 25-ml portions of diethyl ether by shaking gently for 2 to 3 min at each extraction; centrifuge, if necessary, to break any emulsion formed. Filter the combined diethyl ether extracts through cotton-wool (previously washed with diethyl ether) supporting anhydrous sodium sulphate ; wash the filter with a further 10 ml of diethyl ether.Carefully evaporate the combined diethyl ether solution and washings to about 4ml (see Note) and adjust the volume to approximately 5ml with ether. NOTE- diethyl ether solution be evaporated to dryness. Evaporation should be effected a t a temperature 110 higher than 45 "C and on no account must theFebruary, 1975 THE ASSAY OF EPHEDRINE 141 Gas Chromatography The following gas-chromatographic conditions have been found to be satisfactory by the Panel. Column . . .. . . . . Glass or stainless steel; length, 1 m; internal dia- meter, 4 mm (& in). Column packing . . .. . . Chromosorb G, 80-100 mesh, acid washed, DMCS treated, impregnated with 2 per cent. of Carbowax 6000 and 5 per cent. of potassium hydroxide, methanol being used as solvent. Detector . . .. .. . . Flame ionisation. Oven temperature .. . . 150°C. Carrier gas .. .. . . Nitrogen (35 ml min-l). Record chromatograms for three separate 1-pl injections of the final diethyl ether extracts obtained from both sample and standard solutions. Measure peak areas by integration or, alternatively, measure peak heights. From the ratio of the area or height of the ephedrine peak to that of the internal standard peak calculate the ephedrine content of the sample. Detector temperature . . . . 200°C. Injector temperature . . . f 200°C. References 1. 2. 3. 4. 6. 6. Analytical Methods Committee, Analyst, 1948, 73, 312. Welsh, L. H., J. Amer. Pharm. Ass., SC~. Edn, 1947, 36, 373 and 1952, 41, 645. Sanchez, J. A., J. Pharm. Chim., 1935, 22, 489. HorAk, F., and GaSperik, J., Chem. Zvesti, 1957, 11, 558. Chafetz, L., J . Pharm. SC~., 1971, No. 2, 291. Beckett, A. H., and Wilkinson, G. R., J. Pharm. Pkarmac., 1965, 17, 104s.

ISSN:0003-2654    

DOI:10.1039/AN9750000136

出版商:RSC    

年代:1975

数据来源: RSC

摘要:

142 Analyst, Vol. 100 Book Reviews MICROPROBE ANALYSIS. Edited by C. A. ANDERSEN. Pp. xiv + 571. New York, London, A growing realisation of the importance of the distribution, as well as the total amount, of elements present in many matrices over the last two decades has stimulated the analytical scientist into developing analytical techniques that are capable of providing information from restricted volumes of material, which can either be applied to small samples or to the examination of limited regions of larger samples. “Microprobe analysis,”’ edited by C. A. Andersen, collects together seventeen chapters by different authors dealing with subjects relevant to three of the most exten- sively used microprobe techniques, namely the electron, the laser and the ion microprobe. The electron microprobe receives the major coverage, with eleven chapters devoted to instrumentation, principles of X-ray generation, and application to solid-state electronics, geology, ceramics and glass technology, biological materials and analysis of free particulates.Cathodoluminescence and applications of soft X-ray spectroscopy to chemical bonding studies are also considered, with the final chapter dealing with Kossel X-ray diffraction techniques. Chapters on the laser microprobe cover instrumentation and applications to geology, biological materials and metals. Two chapters on the ion microprobe deal generally with instrumentation and applications. The very large amount of information available in the open literature relevant to design and usage of the three types of microprobe covered in this work makes comprehensive coverage im- possible, particularly in the shorter sections on the laser and ion microprobes. Nevertheless, sufficient information is included on principles and technique to give the reader interested in gaining a background on microprobe methods an appreciation of the particular characteristics of the several methods covered and an indication of their likely capabilities.In addition, a number of chapters, notably those on the application of the electron microprobe to geology and to solid- state electronics, and laser microprobe instrumentakion, contain a useful collection of references, which offer a good starting point for more detailled study of particular aspects of microprobe methods.T. B. PIERCE Sydney and Toronto : Wiley-Interscience. 1973. Price Q2.50. X-RAY CRYSTALLOGRAPHY. AN INTRODUCTION TO THE THEORY AND PRACTICE OF SINGLE-CRYSTAL STRUCTURE ANALYSIS. By G. H. W. MILBLTRN. Pp. x + 217. London: Butterworths. 1972. Price i 6 . Dr. Milburn has written this book in order “to provide the reader with the basic knowledge needed to solve crystal structures . . . it should be of interest to final year science students and more specifically to first-year postgraduate crystallogra.phers.” The past few years have seen the appearance of several books on X-ray crystallograpliy with one of two aims in mind. Either they try to form the basis of an introductory course for undergraduate or postgraduate studies, or they offer advice as a handbook to the practising crystallographer. Dr.Milburn has tried to produce a book which, in some measure, does both and in the opinion of this reviewer he has failed in his attempt. This inevitably leads to difficulties in the amount of space to be devoted to each topic, and the book thus suffers from a sad lack of balance. Out of 203 pages of text less than two in the chapter on basic concepts deal with the diffraction of X-rays, and three are given to the precession method in a seventeen-page chapter on the Weissenberg arid precession cameras. There are, however, eleven pages devoted to descriptions of four different commercial four-circle diffractometers, giving information that will be available to purchasers from the manufacturers, while thirteen pages describe computer programs used in X-ray crystallography but give insufficient information to enable the beginner to write his own programs.Unfortunately, there are also lapses in the organisation of material in the book. Thus, in the section on basic concepts, an angle 0 is introduced on page 20 in the discussion on the resolution of the Ku,/Ku, component of X-radiation. On page 23 we again encounter 8 in a discussion on the powder method. I t is not until the Bragg condition is discussed on page 46 that we find out to what the angle refers. The student with “no prior knowledge of the technique” will undoubtedly have been confused long before page 46 reveals all. There are good things within this text, but its faults, combined with its very high price, are great drawbacks to recommending it to students.The main reason for the failure is that too much has been attempted in too short a space. A. D. REDHOUSEFebrzcary , 19 75 BOOK REVIEWS 143 ZEOLITE MOLECULAR SIEVES. STRUCTURE, CHEMISTRY AND USE. Pp. xii + 771. New York, London, Sydney and Toronto: John Wiley & Sons. 1974. Price ,618. Research in the field of zeolite molecular sieves has expanded dramatically over the past 26 years. The birth of this interest was associated with the introduction of synthetic zeolites in commercial quantities and with the discovery of the excellent catalytic properties of these materials in petroleum processing. However, unusually in these days of a surfeit of text-books, mono- graphs, etc., this is the first book to be published in English on this subject.There has been a great need for such a monograph and its publication will be enthusiastically received by all in- terested in these materials. The book has chapters on “Structure,” “Natural Minerals,’’ “Synthetic Zeolites,” “Properties,” “Ion Exchange,” “Adsorption” and “Manufacture” of these materials. There is no chapter on catalysis, the subject of most research with these materials. This omission is a somewhat strange decision of the author, who states that he intends to produce a second book to cover the omission at a later date. The book catalogues many useful properties of zeolites from both published and unpublished sources and will, therefore, be a useful reference book. However the author fails to live up to the sentiments expressed in the poem which heads the preface.Here he states “Long winded writers I abhor” and ends up with “Give me the ones who. . . write what only matters.” This book contains the conclusions from many research papers, which are frequently contradictory and often confusing. However, many errors exist that should have been noticed in the proof reading stage, since some of these mistakes will un- doubtedly confuse the reader who is not completely familiar with the field. This, then, is a book that all workers in this field will use as a very convenient reference book, but there is still a need for a more concise, cheaper, more definitive, work on the subject, which should contain one or more chapters summarising the wealth of information that is available on the catalytic behaviour of these materials.By DONALD W. BRECK. The field still awaits, therefore, a more concise, definitive work on this subject. In a book costing Ll8 one should expect to find few mistakes. L. V. C. REES CHEMICALLY INDUCED DYNAMIC NUCLEAR POLARIZATION. By R. G. LAWLER. Progress in Pp. vi + 145-210. Oxford, The title of this chapter, published as a separate volume, is often abbreviated to CIDNP and may be more familiar in this form. The essential experiment consists in measuring the nuclear magnetic resonance of the products of a free radical reaction during the course of the reaction when very anomalous nuclear magnetic resonance intensities may be observed. The frequencies remain correct but the spectrum may consist of emission, greatly enhanced absorption, or both effects simultaneously present at opposite ends of the spectrum. If the reaction is quenched, the normal intensities grow exponentially with the spin lattice relaxation time, T I .The first clear cases of CIDNP were published in 1967 and much theoretical and experimental work has followed. Ex- periment has shown, and led to the codification of, a wide variety of cases with the behaviour depending on the signs of numerous couplings and splittings in the free radicals, between free radical pairs and in the nuclear magnetic resonance parameters of the product. Most interestingly, the details of the effect depend on whether the radical pairs are formed from the decomposition of a singlet state, e.g., thermal decomposition of diacetyl, or whether the reaction is initiated by a triplet precursor, e.g., photo-excited benzophenone.Although this text covers the experimental work, its emphasis is on the theory of the mech- anisms involved, not an easy task as there are many special cases and some older suggestions which now seem improbable. Basically, two radicals are formed in close proximity, and their initial spin wave function may be that of a singlet state, namely (a /? - pa). If the radicals separate they will then have independent electron spin resonance frequencies, difference 6v, depending on their res- pective g-factors and the nuclear hyperfine couplings and spin states. If they re-encounter each other after a time 7, the wave function will then be (a p) - eisv7 ( pa) and if ~ V T = n, this becomes (rxp + pa), that is, one of the component states of the triplet arrange- ment; this state would be unreactive.Consequently, the relative probability of forming a product by re-encounter or by reaction with the solvent depends on 6v, and hence on the nuclear states involved. Hence the product of recombination will have some nuclear states overpopulated Nuclear Magnetic Resonance Sfiectroscopy, Volume 9, Part 3. New York, Toronto, Sydney and Braunschweig : Pergamon Press. 1973. Price k2.25.144 BOOK REVIEWS Analyst, Vot. 100 and so an abnormal nuclear magnetic resonance spectrum. Conversely, the product from solvent reaction will have an inverse’enhancement and both will have abnormal spectra. This account does not do justice to the complexities of the details, which are all clearly set out by Dr.Lawler. At present it is doubtful if the effect is sufficiently reproducible for use in analysis, but there may be interesting developments for the enhancement of signals from low abundance nuclei. D. H. WHIFFEN ELECTRON MICROSCOPY OF ENZYMES. PRINCIPLES AND METHODS. Volume 2, Edited by M. A. HAYAT. Pp. xviii + 168. London: Van Nostrand Reinhold Co. Ltd. 1974. Price L8-25. Several distinguished scientists have contributed chapters to this book and given their expert views on the location of enzymes in tissues using electron microscopy. Some of these enzymes, e.g., adenylate cyclase, are of current clinical and biochemical interest. Because of the specificity required in their location in the presence of a host of related enzymes, some of them acting on the same substrate as the enzyme to be located, the authors have gone to great lengths to point out how these problems can be overcome.Details are given of novel synthetic substrates, e.g., 6’-adenylyl imidodiphosphate for adenylcyclase, which unlike the natural substrate ATP is not a substrate for ATPases. The product of the reaction, imidodiphosphate, in the form of its lead salt acts as an electron-dense marker. Much useful information is provided on inhibitors and stimulators of each enzyme. Thus alloxan can be used as a specific cyclase inhibitor to prevent the appearance of reaction product when 5’-adenylyl imidodiphosphate is used as a substrate but not the reaction product formed in the presence of ATP. With this degree of sophistication, firm data can be obtained on the location of such enzymes.Workers in the aminoglycoside antibiotic field should note that the book contains methods for the location of acyltransferases and tyrosinase which could usefully be employed in tackling the problems of resistance to such antibiotics and their ototoxicity. Other chapters cover sulphatases (of importance in anti-fouling studies), polyphenoloxidases, haemoproteins and lipases. All are well illustrated, documented and give all necessary practical details. This second volume of the series is recommended for histochemists, bacteriologists, pathologists and all those interested in cellular cytochemistry . S. A. BARKER ALTERNATIVES TO THE LECTURE IN CHEMISTRY. Edited by L. J. HAYNES, P. J. HILLS, C. R. PALMER and D.S. TRICKEY. Proceedings of a Conference held at the University of East Anglia, Norwich, 25 September, 1973. Pp. viii + 89. London: Chemical Society Educational Techniques Subject Group. 1974. Price i:1. The booklet contains the text of eight papers presented, discussion on the papers, and abstracts of papers not presented because of limitations of time. Its value lies in drawing attention to various efforts that are being made to try to ensure that students get more effective courses. Absolute success is difficult to judge, there being so many conclusions and various alternatives outlined, such as: “exciting but confusing;” “no firm conclusion;” “difficult if not impossible to test ;” “results viewed with caution ;” “proven teaching value;” “problem of procrastination is not a new one;” “useful alternative;” etc. It is clear that the lecture will remain for some time to came and that staff and students benefit from multi-channel communication and its honest if inconclusive appraisal. D. THORBURN BURNS RESTRICTED MEDICINES AND POISONS. Compiled by A. W. HUNTER. Pp. 189. London: The Pharmaceutical Press. 1974. Rice fjl.50. This publication contains an annotated list of about 7000 medicines and poisons the sale or supply of which is subject to some legal restriction. The list includes substances and preparations controlled under the Pharmacy and Poisons Act 1933, the Therapeutic Substances Act 1956, the Misuse of Drugs Act 1971 and Section 62 of the Medicines Act 1962, arranged in alphabetical order. The book is a successor to the “Poisons and ‘TSA Guide,” which is now discontinued, and Gumqlative amendments to the list will, as before, be published in The Pharmaceutical Journal. P. C. WESTON

ISSN:0003-2654    

DOI:10.1039/AN9750000142

出版商:RSC    

年代:1975

数据来源: RSC