Identification and quantitative determination of LSD by fluorescence: new data

Sections

ABSTRACT
Introduction
Rapid tests for screening LSD
Differential fluorimetry
Sensitivity
Selectivity
Analysis
Results
Characterization and determination of LSD by synchronous excitation spectrofIuorimetry
Advantages
Analysis
Results
Discussion and conclusions

Details

Author: Ph. BAUDOT , J. C. ANDRE
Pages: 79 to 93
Creation Date: 1985/01/01

Identification and quantitative determination of LSD by fluorescence: new data

Ph. BAUDOT Directeur du groupe d'études et de recherches sur la drogue, Faculté des sciences pharmaceutiques et biologiques, Université de Nancy1, Nancy, France
J. C. ANDRE Maitre de recherches, Département de chimie physique des réactions LA 328 du CNRS, Institut national polytechnique de Lorraine, Nancy, France

ABSTRACT

Tests for the detection of lysergic acid diethylamide (LSD) are not always specific; to cope with this problem the authors have developed a fluorimetric apparatus and technique for the detection and identification of LSD in samples seized from illicit traffic in d rugs. The fluorimeter is not electronic and is simple to make and use, inexpensive, easy to handle and suitable for field analyses. With the new, highly sensitive and selective method of synchronous excitation spectro-fluorimetry, a toxicological analytical laboratory can confirm measurements made in the field and make an immediate determination of the quantity of LSD in the samples seized. The agreement between results obtained using differential fluorimetry or synchronous spectrofluorimetry and chromatographic techniques was found to be excellent. Quantitative analysis is very useful because the amount of LSD per "dose" can vary, from one batch to another, from a few tenths of a μg to several hundred μg.

Introduction

Traffic in and abuse of dependence-producing substances has increased substantially in France in recent years. Only about 1 per cent of the people arrested by the police in connection with drug offences were found to be in possession of lysergic acid diethylamide (LSD), compared with 64 per cent for cannabis and 31 per cent for heroin. Nevertheless, the increase in quantities of LSD seized in France over the past eight years has been considerable [ 1] .

The authors have been interested in developing simple and rapid techniques for the identification of LSD and other drugs of abuse for some time. The detection of accompanying impurities and other hallucinogens in LSD samples is also of importance. If any seized sample is suspected of containing LSD, the LSD concentration should be determined because the content of this drug per "dose" varies enormously 1 from one batch to another, and the use of high doses of LSD may cause severe mental disorders and other complications [ 2] . Therefore, the results of research, particularly the quantitative determination of LSD, should concern not only narcotics laboratory specialists and law enforcement authorities but also physicians and toxicologists working at intensive care units and poison centres as well as educators and other personnel working at assistance and care centres for drug addicts.

Rapid tests for screening LSD

If seized material is suspected of containing LSD, a sample can be screened in the field by people without qualifications in chemistry, using either ultraviolet (UV) irradiation or colour tests. The UV irradiation technique is non-destructive and requires only simple equipment, but it is not specific for LSD as the material might contain many other substances, such as paper, fabric, powder and liquid that would also yield a blue fluorescence. The colour tests marketed in kits are not very specific [ 3] .

Differential fluorimetry

Fluorimetry has long been in use for detecting LSD [ 4] , but fluorimetry performed under the conditions specified by the authors in this article enables the operator to detect the presence or absence of LSD quickly. This technique involves a simple and inexpensive device that can be easily constructed and operated for detecting LSD.

The authors have described elsewhere [ 5] the design of a low-cost field differential fluorimeter that can be used by an unskilled operator on the spot, unlike commercial fluorimeters that are expensive and cumbersome, need a high-tension supply and depend on skilled operators.

1 The term "dose" as employed in statistics on seizures corresponds to a visible subdivision of the illicit sample, such as a sugar lump, a lozenge, a micro-tablet, a pre-cut paper design, but the term is unfortunately not very precise, since it gives no indication of the potency of the product, i.e. the concentration of LSD. Considering that the mean psychoactive dose for a human being is from 0.5 to 1 μg per kg of body weight [ 2] , it is evident that the nature and duration of the effects and possible side effects of a "trip" will not be the same with 20 μg as with 200 μg.

Sensitivity

The extreme sensitivity of this method is ensured by the high fluorescence quantum yield of LSD, which makes it possible to construct a filter fluorimeter that does not need electronics and uses the operator's eye as the measuring device (figure I). Although the eye is not an absolute measuring instrument, it can differentiate and easily compare the colour and intensity of fluorescence of a standard solution of LSD with a solution of an unknown sample suspected of containing LSD. A semi-quantitative determination of LSD can be made by modifying the intensity of the excitatory light reaching the standard solution (assumed to be more concentrated than the solution under investigation), using a mechanical shutter to obtain light intensities that appear equal to the operator. A graph is then used to relate the degree of shutter displacement in millimetres to the concentration of the fluorescent substance under study [ 5] .

Full size image: 36 kB

Selectivity

Selectivity is achieved in the analysis by taking advantage of an interesting spectroscopic property of LSD that the authors have studied : the very pronounced shift in the maximum emission of fluorescence, which is blue in a neutral or acid medium and green in a molar (M) solution of sodium hydroxide (NaOH), as a function of pH [ 6] .

Analysis

For the analysis, samples in the form of pills, tablets, sugar lumps and stars are pulverized, or blotting paper is triturated. Then part of the sample is dissolved in about 5 ml of water or methanol and part in about 5 ml of aqueous M NaOH. After the decantation of insoluble particles, if necessary, the two solutions are placed one after another in the sample cell of the apparatus. The reference cell is filled with a solution of the same solvent in which pure LSD 2 has been dissolved.

Results

If the suspect solution emits no blue fluorescence in a neutral or acid medium, the presence of LSD can be ruled out within the limits of the sensitivity of the test; the minimum detectable concentration is 1.5 x 10 -8g/ml and the minimum detectable quantity about 50 ng. Such negative evidence is very important, for it obviates the need to confiscate for analytical purposes everyday commodities such as powdered milk, medicines or ordinary chemicals and to detain their innocent carriers.

If a positive blue fluorescence is emitted, a follow-up analysis of the M NaOH solution enables some possible interfering factors to be eliminated. Other hallucinogens, such as mescaline, 2-amino-1-(2.5-dimethoxy-4-methyl) phenylpropane (DOM), psilocin, psilocybin, ibogaine and phen- cyclidine also yield a blue fluorescence in aqueous solutions, when excited by UV irradiation although it may be weak for some of them, but without the shift towards green that the presence of LSD produces in an alkaline medium. This is clearly shown in the table.

2 Illicit samples of LSD that have already been analysed and determined by reference techniques can be used for on-the-spot preparation of standard solutions.

Spectroscopic characteristics of main hallucinogens and their possible interference with the fluorescence spectrum of LSD

Full size image: 29 kB, Spectroscopic characteristics of main hallucinogens and their possible interference with the fluorescence spectrum of LSD

To the best of the authors' knowledge, the only sources of true spectroscopic interference are derivatives that possess the base structure of LSD, namely the Δ9 ergoline nucleus. These derivatives may be either lysergic acid amides that are homologous with LSD, such as lysergamide [ [ 13] , [ 14] ] and lysergic acid methylpropylamide (LAMPA) [ [ 15] , [ 16] , [ 17] ], or rye ergot alkaloids, some of which are used as medicaments but whose presence m illicit LSD preparations is unlikely.

Where a positive finding has potential legal or judicial implications, it must be confirmed by a specialized laboratory [ 18] using more sophisticated techniques such as high performance liquid chromatography (HPLC) [ [ 15, 19 - 26] ], gas chromatography/mass spectrometry (GC/MS) [ [ 16] , [ 17] , [ 22] , [ 27] , [ 28] , [ 29] , [ 30] , [ 31] , [ 32] , [ 33] , [ 34] , [ 35] ], infra-red (IR) spectrometry [ [ 21] , [ 29] , [ 34] , [ 36] , [ 37] ] and spectrofluorimetry [ [ 38] , [ 39] , [ 42] ].

Characterization and determination of LSD by synchronous excitation spectrofIuorimetry

Called on for an expert opinion, toxicologists have at their disposal numerous physicochemical methods for the separation, identification and determination of toxic organic substances [ 18] , [ 43] ; the task is to extract as much information as possible from the techniques chosen [ 21] , [ 44] since it would take too long to apply all the techniques. Two mandatory requirements will guide the choice of methods: the specificity of identification and the sensitivity of determination. Maximum sensitivity becomes crucial in certain investigations of addiction-producing preparations (LSD is a prime example in view of the smallness of psychoactive doses).

Among the various spectroscopic techniques currently used in toxicological analysis, molecular fluorescence is one of the most sensitive [ 9] , [ 45] . The fluorescence spectrum of a substance is often characteristic of it, and the intensity of the fluorescence emitted at a given wavelength is an almost linear function of the concentration, provided the concentration is low enough. However, classical spectrofluorimetry has limitations owing not only to imperfections in the apparatus but also to physical factors such as parasitic light. The authors were the first in France to develop a special technique to overcome such limitations. The technique, known as synchronous excitation [ 12] , records a fluorescence spectrum while varying simultaneously (in contrast to the classical method) the excitation and emission wavelengths (λexc and λem) and maintaining between them a constant interval or "step" c (where c = λem - λexc). The choice of a step c is arbitrary, but maximum sensitivity is usually obtained when the step chosen corresponds to the interval between the maxima of the excitation spectrum (λ°exc) and emission spectrum (λ°em) of the substance under investigation. For example, for LSD tartrate in 0.004 M HCl: λ°exc = 323 nm and lamb oem = 433 nm, giving a step c = 110 nm (figure II) and in M aqueous NaOH : lamb oexc = 325 nm and λ°em = 502 nm, thus c = 177 nm [ 6] .

Figure II

Fluorescence spectra of LSD tartrate (10 -6 g/ml in 0.004 M HCI)

Key:

1 Classical excitation spectrum emission wavelength (λem)=433 nm

2 Classical emission spectrum excitation wavelength (λexc)=323 nm

3 Synchronous excitation spectrum with a constant step of 110 nm: c=λ°em-λ°excΔλ1/2=halfheight width of curve (width of emission and excitation slits = 10nm)

Full size image: 23 kB, Figure II

Advantages

This method allows a marked increase not only in the sensitivity of the analysis, which is a sine qua non for the determination of traces of fluorescent molecules, but also in its selectivity ; by improving the definition of the spectra and their characteristic dimensions, namely lamb &ambda;°em and Δλ 1/ 2 (half-height width of the spectrum), it ensures a much more accurate identification of the substance or substances (figure II)- By varying the choice of c, the selectivity of the analysis of mixtures of compounds can be enhanced, particularly when the spectroscopic values of their fluorescence differ widely [ 6] .

Analysis

The sample suspected of containing LSD is treated in the same way as in fluorimetric analysis and is dissolved in two precisely known solvents, water or methanol and M NaOH, to give two stock solutions. These two solutions are decanted or centrifuged, made up to a known volume and then diluted, if necessary, in the same solvent to give the working solutions used for recording the analysis spectra by the synchronous excitation method. The authors made measurements on a commercial model of spectrofluorimeter (JY3C ISA JOBIN & YVON) sold for synchronous excitation work.

Results

Analysis of the characteristics of the fluorescence emission spectrum using synchronous excitation (i.e. the shape of the peak, the value of its maximum λ°em and the half-height width Δλ 1/ 2 of the curve) indicates whether LSD is present by comparison with the control spectra in a neutral or acid medium and an alkaline medium (M NaOH), respectively. A slight shift of the maximum λ°em, the presence of a shoulder in its vicinity and a half-height width Δλ 1/ 2 greater than expected for a given solvent and pH would be reasons for suspecting possible interference by a derivative akin to LSD [ 6] .

All hallucinogens, except for harmine and LSD and its derivatives, generally have similar fluorescence spectra, usually with a singIe wide band in the 310 - 360 nm region, whatever the solvent medium used. Even the spectrum shift observed in an alkaline medium with N,N-dimethyl and diethyltryptamine cannot interfere with the spectrum of LSD (see the tabIe).

Similarly, the spectra of very common drugs such as heroin, morphine and amphetamine cannot cause any interference ; among the alkaloids that are often used, only the spectrum of quinine can mask that of LSD in a neutral or acid but not an alkaline medium.

The height of the fluorescence spectrum obtained at the optimum excitation and analysis wavelengths is proportional to the concentration of LSD, which is determined by reference to a standard control curve- This curve is linear over a range of concentration from 0 to 3 230g of LSD, and the detection limit is about 10 -10 g/ml. However, sensitivity is reduced by a factor of about 50 when an alkaline medium is used.

Discussion and conclusions

The authors' method for the identification of LSD in illicit samples in the field is simple and reliable [ 5] . It uses a very easily operated and inexpensive differential fluorimeter and is based on the observation of fluorescence in two media, neutral or acid and alkaline, to eliminate possible interfering factors. To confirm, if necessary, the analytical findings obtained in the field and to quantify the LSD, laboratories specialized in toxicological analysis can use the synchronous excitation technique of spectrofluorimetry developed by the authors, which is more sensitive and more selective than classical spectrofluorimetry.

The results obtained on suspect samples that were seized recently (see figure III) have shown that agreement is excellent and without false negatives or false positives between, on the one hand, differential fluorimetry and synchronous spectrofluorimetry (performed directly on samples dissolved in two different media) and, on the other hand, the chromatographic techniques that the authors applied in parallel. The latter techniques necessitated prior extraction of the active principle, and they were more cumbersome to put into effect.

Synchronous spectrofluorimetry has the further advantage of giving an easily quantifiable result, which is useful because of the enormous variations in the concentration of LSD from one batch to another. These concentrations of LSD were like those identified in samples seized in the Federal Republic of Germany [ 34] and the United States of America [ 46] . The authors did not detect the presence of other hallucinogens alongside or in place of LSD in any of the seized samples.

The photographs in figure III show some of the illicit samples that were analysed. It can be seen that the "preparations" are carefully executed and varied ; most of them consist of: (a) absorbent paper precut into small designs ; (b) sheets of absorbent card ; or (c) multilayer paper with an absorbent core, often plastic coated and marked out with little squares.

Types l and 2 resemble samples that had been seized in the United States but the pictures, designs, ideograms and ornamentation are different, suggesting that they were manufactured outside the country [ 43] . One common motif was found : the blue dragon. This particular sheet of designs had been found in a letter coming from the United States.

The other samples given to the authors to examine resembled little red six-pointed stars (types 8 and 9) or little brown lentils (type 10) ; these types are also described in reports from the United States. The authors have also dealt with tablets known as "lighter flints'' (type 13), which were common a decade ago in North America [ 47] .

Figure III

Photographs of illicit samples tested for LSD

Key:

A Front side

B Reverse side

1 Type two preparation (see "Discussion and conclusions"), 43 µg of LSD to each small square

2 Type three preparation, 215 µg of LSD to every 5 small squares

3 Type three preparation, 175 µg of LSD to every 10 small squares

4 Type one preparation, 55 µg of LSD to each small design

5 Type two preparation, 240 µg of LSD to each large square on side A

Full size image: 95 kB, Figure III

Figure III (continued)

6 Type three preparation, 40 µg of LSD to each small square on side B

7 Type one preparation, 35 µg of LSD to each design

8 Red six-pointed stars, 81 µg of LSD per star

9 Red six-pointed stars with hole in middle, no LSD

10 Small brown lentils mixed with tobacco, 100 µg of LSD per lentil

11 Yellow tablets stuck between two strips of adhesive tape, no LSD

12 Type three preparation, 20 µg of LSD to each square

13 "Lighter flints", 30 µg of LSD per "flint"

Note: Photographs have been reduced in size. The concentrations of LSD are the averages for several assays performed on several separate aliquots taken at random from each sample.

Full size image: 72 kB, Figure III (continued)

References

01

Toxicomanie et trafic de drogue en France: les statistiques de l'année 1983 (Paris, Office central des stupéfiants, Ministère de l'intérieur et de la décentralisation, 1983).

02

D. V. S. Sankar, LSD : A Total Study (Westbury, New York, PJD Publication Ltd., 1975).

03

Ph. Baudot, J. C. André and J. M. ZiegIer, "Toxicologie analytique du LSD", Annales des falsifications de l'expertise chimique et toxicologique, vol. 73, 1980, pp. 659 - 675.

04

L. A. Dal Cortivo and others, "Identification and estimation of lysergic acid diethylamide by thin layer chromatography and fluorimetry", Analytical Chemistry, vol. 3 8 , 1966, pp. 1959 - 1960.

05

Ph. Baudot and J. C. André, "A low-cost differential fluorimeter for the detection and determination of LSD in illicit preparations", Journal of Analytical Toxicology, vol. 7, 1983, pp. 69 - 71.

06

Ph. Baudot and J. C. André, "Identification and determination of LSD in illicit preparations using synchronous spectrofluorimetry", Analytical Letters, vol. 15 (A 5), 1982, pp. 471 - 492.

07

R. E. Schultes and A. Hofman, The Botany and Chemistry of Hallucinogens (Springfield, Illinois, Thomas R. E. Publication, 1973).

08

A. M. Gillespie, "A spectrofluorimetric study of selected hallucinogens", Analytical Letters, vol. 2, 1969, pp. 609 - 622.

09

M. L. Bastos and S. K. Mule, "Fluorescence in toxicology", in Progress in Chemical Toxicology, A. Stolman, ed., vol. 5 (New York, Academic Press, 1974), pp. 208 - 217.

10

S. G. Hadley, A. S. Muraki and K. Spitzer, "The fluorescence and phosphorescence spectra and phosphorescence decay time of harmine, harmaline, harmalol, harmane and norharman in aqueous solutions and EPA at 77K", Journal of Forensic Sciences, vol. 19, No. 3 (1974), pp. 657 - 669.

11

S. Udenfriend and others, "A spectrophotofluorimetric study of organic compounds of pharmacological interest", Journal of the Pharmacology and Experimental Therapeutics, vol. 120, 1957, pp. 26 - 32.

12

J. C. André, Ph. Baudot and M. Niclause, "Application of synchronous excitation spectrofluorimetry to drug analysis", Clinica Chimica Acta, vol. 76, 1977, pp. 55 - 66.

13

K. Genest, "A direct densitometric method on thin-layer for the determination of lysergic acid amide, isolysergic acid amide and clavine alkaloids in morning glory seeds", Journal of Chromatography, vol. 19, 1965, pp. 531 - 539.

14

A. Hofmann, "Teonanacatl and Ololiuqui, two ancient magic drugs of Mexico", Bulletin on Narcotics (United Nations publication), vol. 23, No. 1 (1971), pp. 3 - 14.

15

G. Megges, "Quantitative Hochdruckflüssigkeitschromatographie von Rauschgiften", Archiv für Kriminologie, vol. 164, Nos. 1 and 2 (1979), pp. 25 - 30.

16

J. H. Siefert and D. L. Collins, "Distinguishing between LSD and LAMPA by capillary GC/MS" Microgram , vol. 17, No. 7 (1984), pp. 100-104.

17

D. T. Stafford, H. S. Nichols and W. H. Anderson, "Efficiency of capillary column GC in separating LSD and lysergic acid methylpropylamide (LAMPA)", Journal of Forensic Sciences, vol. 29, No. 1 (1984), pp. 291 -298.

18

V. Navaratnam and Hoe Kek Fei, "A review of laboratory methods for the analysis of opiates and diluents in illicit drug traffic", Bulletin on Narcotics (United Nations publication), vol. 36, No. 1 (1984), pp. 15 -23.

19

G. W. Chase, "A method for the quantitative analysis of LSD by HLPC", Microgram , vol. 16, No. 7 (1983), pp. 105- 110.

20

R. A. Heacock and others, "A preliminary investigation of the high performance liquid chromatography of some ergot aIkaloids", Journal of Chromatography , vol. 77, 1973, pp.431 -433.

21

I. J. Humphreys, "The work of the drugs intelligence laboratory, home office forensic science service", Bullet in on Narcotics (United Nations publication), vol. 36, No. 1 (1984), pp. 33 - 46.

22

I.Jane and B. B. Wheals, "The characterization of LSD in illicit preparations by pressure-assisted liquid chromatography and gas chromatography", Journal of Chromatography, vol. 84, 1973, pp. 1 81 -1 86.

23

I. S. Lurie, "Forensic drug analysis by HPLC", . International Laboratory, vol. 10, No. 8 (1980), pp. 61 - 65.

24

P.A. MacDonald and others, "Ananalytical studyo f illicit lysergide", Journal of Forensic Sciences, vol. 29, No. 1 (1984), pp. 120 - 130.

25

A.Pryde and M.T. Gilbert, Application of HPLC (London, Chapman and Hall, 1979), pp. 97 -98. .

26

B. B. Wheals, "Forensic aspects of HPLC", Journal of Chromatography , vol. 122, 1976, pp. 8 5 -105.

27

D. J. Marshall, B. A. Petersen and S. P. Vouros, "Some considerations on quantitative methodology and detection limits in organic mass spectrometry", Biomedical Mass Spectrometry, vol. 5, No. 3 (1978), pp. 243 -249.

28

S.Agurell and A. Ohlsson, "Gaschromatography of ergot alkaloids", Journal of Chromatography, vol. 61, 1971, pp. 339-342.

29

K. Bailey, D. Verner and D. Legault, "Distinction of some diakyl amides of lysergic and iso-lysergic acids from LSD", Journal of the Association of Official Analytical Chemists, vol. 56, No. 1 (1973), pp. 8 8 -99.

30

J. Christie, M. W. White and J. M. Wiles, "A chromatographic method for the detection of LSD in biological liquids", Journal of Chromatography, vol. 120, 1976, pp.496 - 501.

31

I. C. Nigam and J. L. Holmes, "Mass spectrometry of lysergic acid diethylamide" Journal of Pharmaceutical Sciences, vol. 58, No. 4 (1969), pp. 506-507.

32

J. Schmidt, R. Kraft and D. Voigt, "Mass spectrometry of natural products, III - Mass spectrometric comparison of lysergic and 9,10-dihydrolysergic acid", Biomedical Mass Spectrometry, vol. 5, No. 12 (1978), pp. 674-678.

33

A.R.Sperling, "Thin-layer and gas chromatographic identification of LSD", Journal of Chromatographic Science, vol.12,1974,pp.265-266.

34

W. Thies, "Zur Analyse von illegalen LSD-Präparaten", Doktorgrad der Biologie von der Universität Hamburg, 1978.

35

R.W.Urich and others, "Mass spectral studies of ultraviolet irradiated and non-irradiated lysergic acid diethylamide extracts from illicit preparations", Analytical Chemistry, vol.47,1975,pp.5 8 1-583.

36

C.C.Cromp and F.G.Turney, "Infrared identification of LSD and related compounds", Journal of Forensic Sciences, vol.12,1967,pp.538-546.

37

J.L.Jacobs, "A simplified method for clean-up and identification (IR) of LSD", Microgram , vol.17,No.6(1984),pp.89-92.

38

J.J. Aaron,L.B.Sanders and J.D. Winefordner, "Analytical study of some important hallucinogens by a combined fluorimetric and phosphorimetric method", Clinica Chimica Acta, vol.45,1973,pp.375-386.

39

R. Canaff, P. Dezan and A. Sperling, "Analysis of hallucinogenic drugs", Journal of Chromatographic Science, vol.10, 1972,pp.268-275.

40

D.H.Fabrick and J.D.Winefordner, "Quantitative measurement of mixtures of hallucinogens by fluorimetry and phosphorimetry", Talanta, vol.20,1973, pp.1220-1223.

41

K.Genest and C.G.Farmilo, "The identification and determination of lysergic acid diethylamide in narcotic seizures", Journal of Pharmacy and Pharmacology, vol.16, 1964,pp.250-257.

42

V.Gillis and T.A.Kubic, "Spectrofluorimetric analysis of illicit drug samples, employing a corrected excitation spectrofluorimeter", I. S, A. Transactions, vol.14,No.3(1975),pp.261-269.

43

G. R. Haislip, "Commerce in drugs and chemicals and the detection of clandestine laboratories", Bulletin on Narcotics (United Nations publication), vol.36,No.l(1984),pp.25-31.

44

J.C.Garcia Fernandez, "Role played by narcotics laboratories in the campaign against drug abuse and drug trafficking: a view from a developing country", Bulletin on Narcotics (United Nations publication), vol.36, No.1 (1984), pp.3-13.

45

S. G. Schulman, Fluorescence and Phosphorescence Spectroscopy: Physico-Chemical Principles and Practice (New York, Pergamon Press, 1977).

46

United States Department of Justice, Drug Enforcement Administration, Office of Science and Technology, Microgram, vol. 15,No.2(1982),pp.12,20,25; vol.15,No.5(1982),p.68;vol.15,No.6(1982),p.84;vol.15,No.7(1982), p.102;vol.15,No.8(1982),pp.122-123;vol.15,No.9(1982),pp.140-141; vol.15, No.10 (1982), p.165; voI.15, No.11 (1982), p.187; vol.15, No.12 (1982),p.207;vol.16,No.l(1983),p.218;vol.16,No.2(1983),pp.21-22; vol.16, No.3 (1983), pp.41-42; vol.16, No.4(1683),p.60; vol.16, No.5 (1983),pp.72-73;vol.16,No.6(1983),p.87;vol.16,No.7(1983),pp.99,100, 105;vol.16,No.8(1983),pp.115-116;vol.16,No.9(1983),p.138,vol.16, No.10(1983), p.148;vol.16,No.11 (1983), p.157;vol.17,No.4(1984), pp.49-50;vol.17,No.6(1984),p.82;vol.17,No.7(1984),p.93;vol.17, No.9(1984),p.123.

47

Bureau des drogues dangereuses, Ministère santé et bien-être social du Canada, Montréal, Communication personnel,1982.