MICROCHEMICAL IDENTIFICATION OF SYNTHETIC NARCOTICS

Sections

EXPERIMENTAL MATERIALS
METHOD
PHOTOGRAPHY
PHOTOGRAPHS (unless otherwise marked, the total enlargement is 275X)
RESULTS AND CONCLUSIONS

Details

Author: CHARLES G FARMILO , R.J. ROSS , STAVELY BERRY, , PATRICIA M. L. KENNETT
Pages: 21 to 31
Creation Date: 1950/01/01

MICROCHEMICAL IDENTIFICATION OF SYNTHETIC NARCOTICS

AMIDONE a, HEPTALGIN b, DEMEROL c, PIPIDONE d

CHARLES G FARMILOe
R.J. ROSSf
STAVELY BERRY,e
PATRICIA M. L. KENNETTe

The method of identification of organic basic compounds by means of characteristic crystals under the microscope was developed by Behrens,[2] Wormley,[13] Stevenson,[11] Fulton,[4 ] Amelink,[1] et al.; and is now conceded to be the most reliable means of identifying the pure alkaloids met with in drug analysis and toxicology. In the following article a number of photographs illustrate some characteristic crystals which may be used for identification purposes. The reagents are for the most part described in articles by the following authors: Ami-done has been studied quite thoroughly by Fulton,s Watson and Bowman,[12] Schuldiner,[9 ] Lucas[8] and others; demerol by Levine,[7] Ducloux,[3] and Hanson;[6] heptal-gin and "pipidone" were studied as part of a general project on the identification of narcotics being carried on at present in the Food and Drug Laboratories in Ottawa. Details Of our work will be published at a later date. The pictures* nearly all represent crystals which have never been published, although the reagents may have been given previously by other workers.

a Amidone hydrobromide : 6-dimethylamino-4,4-diphenyl-heptanone-3 hydrobromide.

b Heptalgin : 6-morpholinyl-4,4-diphenylheptanone-3 hydro-chloride.

cDemerol hydrochloride, Brand of Meperidine hydrochloride: ethyl- 1-methyl-4-phenylpiperidine-carboxylate.

d P.1.-S.1, "Pipidone" : 6-piperidine-4,4-diphenyl-5-methyl-hexanone-3 hydrochloride.

e Chemists employed at Organic Chemistry and Narcotic Section, Food and Drug Divisions, Department of National Health and Welfare, 35 John Street, Ottawa, Canada.

f Supervisor, Technical Research Department, National Film Board, Ottawa, Canada.

* The photomicrography in this paper was the work of Roger J. Ross.

EXPERIMENTAL MATERIALS

The narcotics investigated in this paper were gifts obtained from the following sources: Amidone hydrobromide, E. B. Shuttleworth and Co. Ltd., Toronto, Canada; Heptalgin, Glaxo Laboratories Ltd., Research Division, Greenford, Middlesex, England; P.1.-S.1 ("Pipidone") Burroughs Wellcome & Co. 183-193 Euston Road, London, N.W. 1, England; Demerol hydro-chloride, Winthrop Chemical Co. Inc., Windsor, Ontario. These gifts are hereby gratefully acknowledged.

METHOD

The method of producing the crystals was the usual one of adding a drop of the aqueous solution of alkaloidal salt to a flat microscope 'slide, and then adding a drop of the appropriate reagent, sometimes mixing with a stirring rod, sometimes not. A cover glass was used, in some cases, and was placed over the alkaloid drop. The reagent drop. was then placed at the edge of the circle so that it was drawn into the alkaloid drop by capillary action. This caused faster crystal growth in solutions which had low surface tension, since spreading and rapid drying of the reaction drop on the slide were prevented.

PHOTOGRAPHY

There are one or two novel features about the photography which are worth mentioning. The conventional photographic set-up employed a Bausch and Lombe, Model L. Camera and a Spencer microscope. The ocular was a 10X normal Spencer, with a 10X objective, and in a few cases a 20X objective, with a 25 3/8 in. belows extension. The total enlargement is 275 times or 575 times. The microscope was set up for 10X objective with Kohler critical illumination for low magnification (see standard text-books). All crystals except those with a red colour were photographed with a Wratten No. 61 green filter using a Tungsten ribbon filament lamp.

A few photomicrographs made more recently than the others were taken with a zircon arc micrscope lamp in- stead of the ribbon filament used previously. This gave about fifty times as much light for photography, as measured on the ground glass by a Photo-volt, Model 200, sensitive light meter. The light readings for the first set were about 0.04 units, while those for the second set were about 2.0 units, both measured with the Wratten No. 61 green filter in place. The exposure time under these latter conditions was found about 1/25 sec.

The photos were taken on 5" x 7" super XX Kodak film developed in a modified D-76 developer for 7 minutes.

PHOTOGRAPHS (unless otherwise marked, the total enlargement is 275X)

    Amidone (hydrobromide)
  1. Solution 8 (1:400) with iodine in 10 per cent HBr (575X).

  2. 1 per cent with iodine in 10 per cent HBr.

  3. 0.05 per cent with HgBr 2 and HCl.

  4. 1 per cent with Mayer's and KI.

  5. 1 per cent with Bouchardat No. 1.

  6. 1 per cent with Bouchardat No. 10.

  7. Solution 4 (1:800) with H 2PtCl 6and HCl.

  8. Solution 8 (1:400) with gold cyanide reagent.

  9. 1 per cent with HgCl 2.

  10. 1 per cent with HgCl 2.

  11. 1 per cent with HgCl 2and NaCl and NaOAc.

  12. 0.05 per cent with HgCl 2 and NaCl and NaOAc.

  13. 1 per cent with Hg(CN) 2 and NaI.

  14. 0.05 per cent with Hg (CN) 2and NaI.

  15. 1 per cent with FeCl 3 in HCl.

  16. 1 per cent with FeC1 3in HCl

  17. 1 per cent with UO 2Cl 2and HCl.

  18. 1 per cent with UO 2Cl 2 and HCl.

  19. 1 per cent with zinc hydrobromic acid.

  20. l per cent with zinc hydrobromic acid (575X).

  21. 1 per cent with NH 4ClO 4(575X).

  22. Heptalgin
  23. 2per cent with stannous H Bromide.

  24. Demerol (hydrochloride)
  25. 2 per cent with Dragendorff 's reagent.

  26. 0.4 per cent with Reinecke's salt.

  27. 2 per cent with K 3Fe (CN) 6.

  28. With H 2PtCl 6.

  29. Pipidone
  30. 1 per cent with Millon's reagent.

  31. 1 per cent with Millon's reagent.

RESULTS AND CONCLUSIONS

Most of the crystals given are very easily obtained, and are examples of the kind of microchemical reaction that can be used for identification of these and similar compounds. However, only one crystal test was dis- covered for "Pipidone", the one with Millon's reagent which is pictured. Amidone has now been thoroughly studied by different investigators, and Demerol fairly well. Further work is being carried on with the compounds Heptalgin and "Pipidone".

1. Amidone with iodine in 10 per cent hydrobromic acid. Shows the three types of crystals that form in the same test drop: deep red grains, pale yellow plates, and white flakes (high magnification)

Full size image: 138 kB, 1. Amidone with iodine in 10 per cent hydrobromic acid. Shows the three types of crystals that form in the same test drop: deep red grains, pale yellow plates, and white flakes (high magnification)

2. Amidone with iodine in 10 per cent hydrobromic acid. Shows the white flakes (the prevalent type of crystal with this reagent) forming from the amorphous precipitate

Full size image: 105 kB, 2. Amidone with iodine in 10 per cent hydrobromic acid. Shows the white flakes (the prevalent type of crystal with this reagent) forming from the amorphous precipitate

3. Amidone with mercuric bromide and hydrochloric acid. Colourless-white feathered plates

Full size image: 121 kB, 3. Amidone with mercuric bromide and hydrochloric acid. Colourless-white feathered plates

4. Amidone with Mayer's and potassium iodide

Full size image: 168 kB, 4. Amidone with Mayer's and potassium iodide

5. Amidone with Bouchardat Reagent No. 1

Full size image: 159 kB, 5. Amidone with Bouchardat Reagent No. 1

6. Amidone with Bouchardat Reagent No. 10. The appearance is characteristic of a moderately concentrated amidone solution (1 percent in this case) the squarish grains are due to the potassium iodide of the reagent

Full size image: 120 kB, 6

6. 7. drop

Full size image: 154 kB, 6. 7. drop

8. Amidone with gold cyanide reagent

Full size image: 131 kB, 8. Amidone with gold cyanide reagent

9. Amidone with mercuric chloride. Shows crystal-groups forming from the amorphous precipitate

Full size image: 80 kB, 9. Amidone with mercuric chloride. Shows crystal-groups forming from the amorphous precipitate

10. Amidone with mercuric chloride. Crystallization further advanced

Full size image: 96 kB, 10. Amidone with mercuric chloride. Crystallization further advanced

11. Amidone (1 percent with mercuric chloride, sodium chloride and sodium acetate

Full size image: 69 kB, 11. Amidone (1 percent with mercuric chloride, sodium chloride and sodium acetate

12. Amidone (0.05 per cent) with mercuric chloride, sodium chloride and sodium acetate

Full size image: 47 kB, 12. Amidone (0.05 per cent) with mercuric chloride, sodium chloride and sodium acetate

13. Amidone (1 per cent) with mercuric cyonide and sodium iodide

Full size image: 115 kB, 13. Amidone (1 per cent) with mercuric cyonide and sodium iodide

14. Amidone (0.05 per cent) with mercuric cyanide and sodium iodide

Full size image: 84 kB, 14. Amidone (0.05 per cent) with mercuric cyanide and sodium iodide

15. Amidone with ferric chloride in hydrochloric acid. Brown yellow crystals

Full size image: 53 kB, 15. Amidone with ferric chloride in hydrochloric acid. Brown yellow crystals

16. Amidone with ferric chloride in hydrochloric acid. A slightly different type of crystal formation

17. Amidone with acid uranium chloride reagent. This type of crystal forms is nearly round rosettes of plates

Full size image: 35 kB, 17. Amidone with acid uranium chloride reagent. This type of crystal forms is nearly round rosettes of plates

18. Amidone with acid uranium chloride reagent. These irregular straggling crystals form in the same test drop as the rosette crystals of the preceding picture. Both types are large, yellow-coloured crystals.

Full size image: 49 kB, 18

19. Amidone with zinc hydrobromic acid

Full size image: 164 kB, 19. Amidone with zinc hydrobromic acid

20. Amidone with zinc hydrobromic acid. A group of crystals under high magnification

Full size image: 111 kB, 20. Amidone with zinc hydrobromic acid. A group of crystals under high magnification

21. Amidone with ammonium perchlorate (high magnification)

Full size image: 102 kB, 21. Amidone with ammonium perchlorate (high magnification)

22. Heptalgin with acid stannous bromide

Full size image: 101 kB, 22. Heptalgin with acid stannous bromide

23. Demerol with Dragendroff’s reagent

Full size image: 115 kB, 23. Demerol with Dragendroff’s reagent

24. Demerol with Reinecke’s salt

Full size image: 81 kB, 24. Demerol with Reinecke’s salt

25. Demerol with chloroplantinic acid (this picture supplied by the Secretariat)

Full size image: 132 kB, 25. Demerol with chloroplantinic acid (this picture supplied by the Secretariat)

26. "Pipidone" with Millon’s reagent

Full size image: 69 kB, 26.

27. "Pipidone" with Millon’s reagent

Full size image: 117 kB, 27.

28. "Pipidone" with Millon’s reagent

Full size image: 94 kB, 28. 1

Behrens, H., Anleitung zur mikrochemischen Analyse, vol. iii, 1st Edition, 1896.

2

Amelink, F., Schema zur mikrochemischen Identifikation von Alkaloiden, Amsterdam 1934.

3

Ducloux, E. H., Notas Microquimicas sobre 'Doping'. Buenos Aires (1943).

4

Fulton, C. C., American Journal of Pharmacy, 112, 1-35 (1940); ibid., 104, 244-271 (1932).

5

Fulton, C. C., "Identification of Methadone by Microcrystals" United Nations document E/CN.7/ll7, pp. 17-31, 27 Feb. 1948.

6

Hanson, Arne, Svensk Kemisk Tidskrift, 58, 10-23 (1946).

7

Levine, Joseph, Industrial and Engineering Chemistry, Analytical Edition, 16, 408-10 (1944).

8

Lucas, G. H. W., Detection of Amidone, Dept. of Pharmacology, University of Toronto, Canada.

9

Schuldiner, Jacob A., Analytical Chemistry, 21, 298-300' (1949).

10

Shiltaber, C. P., Photomicrography in Theory and Practice, John Wiley and Sons, New York, 1944, pp. 93, 730.

11

Stevenson, C. H., Some Microcbemical Tests for Alkaloids, J. B. Lippincott Co. Philadelphia, 1921.

12

Watson, R. C., and Bowman, M. I., Journal of the American Pharmaceutical Association, 38, 369-373 (1949).

13

Wormley, T. G., Microcbemistry of Poisons, Philadelphia, 1869