PRACTICAL PROCEDURE
DISCUSSION
SUMMARY
Author: E. G. C. Clarke
Pages: 27 to 44
Creation Date: 1959/01/01
Although the quest for a substance that will relieve pain is nearly as old as civilization, for centuries opium remained the only analgesic of importance, the part played by such substances as alcohol, hemp, henbane and mandragora being relatively slight. The first significant advance was the isolation of morphine by Serturner in 1803. With the discovery of this powerful analgesic of constant and reproducible properties the search might, indeed, have ended. However, the introduction of morphine had the additional effect of emphasizing the less desirable properties of narcotic drugs. Consequently, subsequent research was directed towards the production of a substance which, while possessing the analgesic action of morphine, was neither toxic nor liable to cause addiction. Initially, experiments designed to modify the morphine molecule resulted in the production of such substances as diacetylmorphine (heroin, 1900), dihydromorphinone (dilaudid, 1923) and methyl-dihydromorphine (metopon, 1937). The introduction of pethidine, the first entirely synthetic analgesic, in 1939, marked the next important advance. This discovery was soon followed by the introduction of a large number of similar substances. In spite of this, none of the compounds so far produced has been judged sufficiently free from habit-forming properties to merit exemption from international narcotic control. Some idea of the numbers involved can be obtained from the following figures. In 1928, 11 drugs were controlled; in 1938, 18; in 1948, 19; and in 1958, no fewer than 65.
Once a drug has been brought under international control, its absolute identification becomes a matter of prime importance. Owing to the penalties attached to its illegal possession or use, this identification must be a matter of complete certainty. This fact has long been realized, and many tests for the older analgesics have been described. In the last few years, however, the spate of new compounds flooding on to the market has made this identification extremely laborious. Not only has the number of analgesics increased, but hundreds of other alkaloidal substances such as antihistamines and local anaesthetics have become available. As there is no way, short of absolute identification, in which an analgesic can be differentiated from any other basic drug, the forensic analyst is nowadays faced with an almost impossible task, and must carry out a multiplicity of tests before he can make his diagnosis.
Although it is essential to have some method by which any analgesic (or, ideally, any alkaloidal substance) can be identified, with few exceptions tests have been described only for the better-known analgesics. It is not proposed to review these tests in detail, although mention may be made of x-ray diffraction patterns (Barnes, [1] ; Barnes & Sheppard, [2] ), ultra-violet spectra (Oestreicher, Farmilo & Levi, [3] ; Breinlich, [4] ), infra-red spectra (Levi, Hubley & Hinge, [5] ), paper chromatography (Curry & Powell, [6] ; Vidic, [7] ; Goldbaum & Kazyak, [8] ) and crystal and colour tests (Farmilo, Levi, Oestreicher & Ross, [9] ; Levi, [10] ; Farmilo & Levi, [11] ; Brandstratter, [12] ; Vidic, [13] ; and Lampe, [14] ). It is the purpose of this paper to describe crystal and colour tests for microgram quantities of 51 analgesic drugs.
As some confusion exists in the literature as to the nomenclature of these substances, they are listed in table 1. From the analytical point of view, these compounds may be divided into five groups as follows:
The morphine group. This may be further subdivided into two sections: ( a) those substances in which the phenolic group is free as in morphine; ( b) those in which it is masked, as in codeine and heroin.
The morphinan group.
The pethidine group. This may be subdivided into ( a) the esters and ( b) the reversed esters, although such division does not include ketobemidone. A third sub-group, 3 ( c), contains substances in which a hexamethyleneimine ring replaces the pyridine ring.
The methadone group. This may be subdivided into ( a) the alcohols and ( b) the ketones.
Miscellaneous compounds, mainly butane derivatives. This group includes the dialkylthiambutenes.
For the sake of completeness, the narcotic antagonists nalorphine and levallorphan have been included in their respective groups.
Microcrystalline tests. The hanging microdrop technique developed by Clarke & Williams ([15] , [16] ) is used. This method has now been applied successfully to various groups of nitrogenous bases, including, in addition to plant alkaloids, local anaesthetic, antihistamine, antimalarial, and sympathomimetic drugs (Clarke, [17] , [18] , [19] , [20] , [21] ; Williams, [22] ). Briefly, this technique consists in transferring a microdrop (volume approximately 0.1µl) of the test solution to a cover slip by means of a glass rod 1 mm in diameter. A similar drop of reagent is now added, and the two mixed, the glass being scratched with the rod to encourage crystallization. A cavity slide is ringed with 25% gum arabic solution, inverted and pressed down on the cover slip, and reinverted. The hanging drop is examined under low magnification, and any precipitate, crystalline or otherwise, recorded. The drop is re-examined at intervals during the next forty-eight hours.
2. The morphinan group. Members of this group give a blue colour, turning to green, with the sulphuric acid-molybdate reagent. A similar colour is seen with certain morphine derivatives, but the fact that the morphinans give no colour with the Marquis reagent distinguishes them from the latter group. The phenols give a yellow colour with nitric acid, while the methoxy derivatives do not. The diazo test described above also shows the phenolic group.
Approved name |
Common name |
Chemical name |
Approved name |
Common name |
Chemical name |
---|---|---|---|---|---|
Group 1 a |
|
|
Group 3 b |
|
|
Deso-morphine |
Permonid |
Dihydro-deso-xymorphine |
Morpheridine |
Morpholinoethyl- norpethidine |
l-(2-morpholinoethyl)-4-phenyl-piperidine-4- carboxylic acid ethyl ester |
Methyl-desorphine |
|
6-methyl- Δ 6-desoxymorphine |
Pethidine |
Meperidine Dolantin |
1-methyl-4-phenylpiperidine-4-carboxylic acid ethyl ester |
Methyl-dihydro-morphine |
|
6-methyl-dihydro-morphine |
Properidine |
Spasmodolisine |
1 -methyl-4-phenyl-piperidine-4-carboxylic acid isopropyl ester |
Metopon |
|
Methyl-dihydro-morphinone |
Trimeperidine |
Promedol |
1-2-5-trimethyl-4-phenyl-4-propionoxy piperidine |
Morphine-N-oxide |
Genomorphine |
Morphine-N-oxide |
Group 3 c |
|
|
Nalorphine |
Lethidrone |
N-allyl-nor-morphine |
Ethoheptazine |
W401 Zactane |
1-methyl-4-carbethoxy-4-phenyl-hexamethyl-cneimine |
Normorphine |
|
De-N-methyl-morphine |
Proheptazine |
W757 |
1,3-dimethyl-4-phenyl-4-propionoxy-hexamethyl-cneimine |
Oxy-morphone |
Numorphan |
Dihydro-hydroxy-morphinone |
|
|
|
Group 1 b |
|
|
Group 4 |
|
|
Acethyl-dihydro-codeine |
Acetylcodone |
Acetyldihydrocodeine |
Alphacetylmethadol |
Methadyl acetate |
α-4,4-diphenyl-6-dimethyl-amino-3-acet oxyheptane |
Myrophine |
Myricodine |
Myristyl ester of Benzyl-rnorphine |
Alphamethadol |
Amidol |
α-4,4-diphenyl-6-dimethyl-aminoheptanol-3 |
Norcodeine |
|
De-N-methylcodeine |
Dipipanone |
Pipadone |
4,4-diphenyl-6-piperidino-3-heptanone |
Pholcodine |
Ethnine |
β-4-morpho-linylethyl-morphine |
Isomethadone |
Isoamidone |
4,4-diphenyl-5-methyl-6-4imethyla minohexanone-3 |
Thebacon |
|
Acetyl-dihydro-codeinone |
Methadone |
Amidone Physeptone |
4,4-diphenyl-6-dimethyl-aminoheptanone-3 |
Group 2 |
|
|
|
|
|
Dextro-methorphan |
Romilar |
(+)-3-methoxy-N-methyl-morphinan |
Normethadone |
Ticarda |
4,4-diphenyl-6-dimethyl-amino-3-hexanone |
Dextrorphan |
|
(+)-3-hydroxy-N-methyl-morphinan |
Phenadoxone |
Heptalgin |
4,4-diphenyl-6-morpholinoheptanone-3 |
Levallorphan |
Lorfan |
(-)-3-hydroxy-N-allyl morphinan |
|
|
|
Levo-methorphan |
|
(-)-3-methoxy-N-methyl-morphinan |
Group 5 |
|
|
Levo-rphanol |
Dromoran |
(-)-3-hydroxy-N-methyl-morphinan |
Dextromoramide |
R875 |
(+)-3-methyl-2,2-dipheny1-4-morpholino-butyryl- |
Pheno-morphan |
|
3-hydroxy-N-phenethyhl-morphinan |
Diethylthiambutene |
Themalon |
3-diethylamino-1,1-di-(2'-thienyl)-1-butene |
Race-methorphan |
|
(±)-3-methoxy-N-methyl-morphinan |
Dimethylthiambutene |
|
3-dimethylamino-1,1-di-(2-thienyl)-1-butene |
Race-morphan |
Citarin |
(±)-3-hydroxy-N-methyhl-morphinan |
Dioxaphetyl butyrate |
Amidalgon |
4-morpholino-2,2-diphenylethyl butyrate |
Group 3 a |
|
|
Ethyhnethylthiambutene |
|
3-ethylmethylamino-1,1-(2'-thienyl)-l-butene |
Alpha-meprodine |
|
α-l-methyl-3-ethyl-4-phenyl-4-propionoxy piperidine |
Levomoramide |
|
(-)-3-methyl-2,2-diphenyl-4-morpholino-butyryl- pyrrolidone |
Alphaprodine |
Nisentil |
α-1,3-dimethyl-4-phenyl-4-propionoxy-piperidine |
Propoxyphene |
Doloxene |
4-dimethylamlno-1,2-diphenyl-3-methyl-2-propio noxy butane |
Anileridine |
|
1 -[2-(p-aminophenyl)-ethyl ]-4-phenyl-piperidine-4- carboxylic acid ethyl ester |
Racemoranaide |
|
(±)-3-methyl-2,2-diphenyl-4-morpholino-butyryl-pyrrolidone |
Beta-meprodine |
|
a-l-methyl-3-ethyl-4-phenyl-4-propionoxy-piperidine |
Tolpronine |
Proponesin |
α- Δ 3 -piperideino-B-hydroxy-y-ortho-toloxy-pro pane |
Betaprodine |
|
β-1,3-dimethyl-4-phenyl-4-propionoxy-piperidine |
- |
3570CT |
Piperidino methyl-2-benzoyl-7-benzodioxan |
Etoxeridine |
|
1-[2-(2-hydroxyethoxy)-ethyl]-4-phenyl-piperidine-4--carboxylic acid ethyl ester |
- |
3638CT |
Piperidinomethyl-2-p-met hoxybensoyl-7-benzo dioxan |
Hydro-xypethidine |
Bemidone |
1-methyl-4-(3-hydroxyphenyl)-piperidine -4-carboxylic acid ethyl ester |
- |
3633CT |
Morpholinomethyl-2-benzoyl-7-benzodioxan |
Keto-bemidone |
Cliradon |
4-(3-hydroxyphenyl)-l-methyl-4-piperidyl ethyl ketone |
- |
3639CT |
Morpholinomethyl-2-p-methoxybenzoyl-7-benzo dioxan |
The substances tested were dissolved in 1% acetic acid, with the following exceptions. Levorphanol, levomethorphan, racemorphan, racemethorphan, levallorphan, phenomorphan, nalorphine, levomoramide, dextromoramide, and racemoramide were dissolved in 1% hydrochloric acid; myrophine was dissolved in 90% methanol and ketobemidone in both 1% acetic acid and syrupy phosphoric acid. Details of the reagents employed are given in appendix A.
The results are recorded in tables 2 and 3. Table 2 gives the type of precipitate obtained when a drop of a 1% solution of the substance is mixed with a similar drop of reagent, giving in effect a 1 in 200 solution. This table will often enable a tentative identification to be made, but too rigid an adherence to it must be avoided. Traces of organic matter will often inhibit crystallization, while, on the other hand, exceptionally favourable circumstances will sometimes cause crystallization of precipitates that are normally amorphous.
Table 3 gives descriptions of the various crystals obtained, those most suitable for the purpose of identification being printed in small capitals. In selecting these tests, various points have been considered; not only the sensitivity, but the speed and certainty with which the crystals form, as well as their dissimilarity to crystals produced by closely related compounds with the same reagent, have been taken into account. These results are discussed in more detail later.
Some of the crystals obtained are illustrated in plates 1-24.
2. Colour tests. These are carried out with microdrops on opal glass as described previously. In the case of the Marquis test, a microdrop of the test solution is evaporated to dryness and the residue moistened with a microdrop of a solution of 1 part of 40% formaldehyde in 20 parts of concentrated sulphuric acid. For Mandelin's, Frohde's, Mecke's and Reichard's tests, a microdrop of the test solution is mixed with a microdrop of an aqueous solution of the oxidizing agent (0.5% ammonium vanadate (Mandelin), 0.5% ammonium molybdate (Frohde), 0.5 % selenium dioxide (Mecke) and 1% sodium tungstate (Reichard)). After evaporating to dryness, the residue is moistened with a microdrop of concentrated sulphuric acid, and the colour changes noted.
Vitali's test is carried out by evaporating a microdrop of the test solution to dryness, and adding a microdrop of fuming nitric acid. The colour is noted and the acid evaporated to dryness. The colour is again noted, and yet again after moistening with an ethanolic solution of potassium hydroxide.
Another colour test that is sometimes of value in differentiating between free and masked phenolic groups (e.g., morphine and codeine, levorphanol and levomethorphan) is the microdiazo test. A microdrop of a saturated solution of p-nitro-aniline is placed on opal glass, and microdrops of 1% sodium nitrite solution, the test solution, and 2N sodium hydroxide solution added in that order. Phenols give red or purple colours. The same test may be used to identify substances containing a primary arylamino group. Thus if to a microdrop of a solution of anileridine in 2N hydrochloric acid is added a similar drop of 1% sodium nitrite solution, followed by one of an alkaline solution of β-naphthol, a red colour will be produced. The sensitivity of the microdiazo test is about 0.25μg.
The results obtained are shown in tables 4 and 5, and discussed below.
The identification of a narcotic drug presents special difficulties for the analyst. In the case of an ordinary alkaloidal substance, a provisional identification may be confirmed by comparison of crystals formed from the test material with those formed from a known sample of the suspected drug and the same reagent. In the case of a narcotic drug this may not always be possible, owing to the difficulty of obtaining specimens of these compounds. Thus while most laboratories engaged in this type of work will have morphine and pethidine available for use as controls, few are likely to possess such substances as properidine or dimethylthiambutene. And while it may be argued that these compounds are so uncommon that the question of their identification is unlikely to arise the fact remains, none the less, that they are controlled narcotic drugs, and that the clandestine manufacture and use of any synthetic chemical is possible, however improbable.
It is therefore essential that the final identification should be based on as many types of test as possible. X-ray diffraction patterns and ultra-violet and infra-red spectra should be obtained if the necessary apparatus is available. Rf values, and, if sufficient material is available, the ordinary physical constants such as melting point should be ascertained. Finally, crystal and colour tests should be carried out, and the results compared with those given in the tables.
In order to help in the application of these tables, they are now discussed group by group in greater detail.
1. The morphine group. All members of this group give varying shades of purple or violet with the Marquis reagent, but it is not usually practicable to pinpoint any particular derivative by the exact shade given. A transient yellow colour is sometimes seen before the purple develops. It must be realized that this purple colour with the Marquis reagent is in no way confined to members of the morphine group, since some of the pethidine group give a similar colour, as also do numerous phenothiazine derivatives such as chloropromazine (Clarke, [20] ). The colours given with the other reagents will in some cases help in identification. In particular, the microdiazo test serves to pick out those compounds with a free phenolic group.
With regard to the crystal tests shown in table 3, most of these compounds give a number of crystalline precipitates that will serve as tests. Desomorphine, however, gives crystals with only one of the ordinary reagents (plates with mercuric.chloride) although it will also give fans of needles with the chloromercuric acid reagent described by Fulton ([23] ).
1 Gold bromide
2 Gold bromide / hydrochloric acid
3 Gold chloride
4 Lead iodide
5 Mercuric chloride
6 Pciric acid
7 Platinum chloride
8 Platinum iodide
9 Potassium bismuth iodide
10 Potassium cadimum iodide
11 Potassium chromate
12 Potassium iodide
13 Potassium mercury iodide
14 Potassium permanganate
15 Potassium tri-iodide (1)
16 Potassium tri-iodide (2)
17 Potassium tri-iodide (3)
18 Sodium carbonate
19 Sodium phosphate
20 Zinc chloride
21 Trinitrobenezoic acid
22 Patinum bromide
23 Picrolonic acid
24 Styphnic acid
25 Di-sodium methylarsonate
26 Potassium cyanide
27 Ammonium thiocyanate
ALKALOID/Reagent |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
16 |
17 |
18 |
19 |
20 |
21 |
22 |
23 |
24 |
25 |
26 |
27 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Group 1a |
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|
Desomorphine |
a |
a |
a |
a |
x |
a |
a |
a |
a |
a |
a |
- |
a |
a |
o |
- |
o |
- |
- |
- |
- |
a |
a |
a |
- |
- |
- |
Methyldesorphine |
a |
a |
o/a |
a |
x |
x |
a |
a |
x |
a |
x |
- |
a |
a |
o |
a |
o |
a |
x |
- |
a |
a |
a |
a |
x |
a |
- |
Methyl-dihydro-morphine |
a |
x |
o/a |
- |
o |
x |
x |
x |
x |
x |
- |
- |
x |
a |
o |
- |
o |
- |
- |
- |
- |
x |
- |
x |
- |
- |
- |
Metopon |
a |
a |
a |
- |
o |
a |
a |
a |
x |
a |
- |
- |
a |
a |
o |
o |
x |
x |
- |
- |
- |
a |
x |
a |
x |
- |
- |
Morphine-N-oxide |
o |
o |
a |
- |
- |
x |
x |
a |
a |
a |
- |
- |
a |
a |
o |
- |
x |
- |
- |
- |
- |
a |
- |
a |
- |
- |
- |
Nalorphine |
a |
a |
o |
- |
a |
a |
a |
a |
a |
a |
x |
- |
x |
a |
x |
- |
x |
- |
- |
- |
- |
a |
a |
a |
- |
- |
- |
Normorphine |
x |
x |
a |
- |
- |
x |
a |
a |
x |
x |
a |
- |
x |
a |
o |
- |
o |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Oxymorphone |
x |
x |
a |
- |
x |
a |
- |
a |
a |
- |
- |
- |
o/a |
a |
o |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
- |
Group 1b |
|
|
|
|
|
|
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|
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|
|
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|
|
Acteyl-hydro-codeine |
a |
x |
x |
x |
a |
x |
x |
a |
a |
a |
- |
- |
a |
- |
a |
- |
a |
- |
- |
- |
- |
o/a |
x |
a |
- |
- |
- |
Myrophine |
a |
a |
a |
a |
a |
a |
a |
a |
a |
a |
o |
a |
a |
a |
o |
x |
o/a |
o |
o |
- |
x |
a |
x |
a |
o |
o/a |
o/a |
Norcodeine |
x |
x |
x |
- |
- |
o/a |
a |
a |
a |
x |
x |
x |
x |
a |
o |
- |
o |
- |
- |
x |
- |
a |
a |
a |
- |
- |
x |
Pholcodeine |
a |
a |
a |
a |
- |
a |
x |
a |
x |
a |
- |
- |
a |
a |
o |
- |
o |
- |
- |
- |
- |
a |
a |
x |
- |
- |
- |
Thebacodeinme |
x |
x |
x |
a |
x |
x |
a |
a |
a |
x |
x |
- |
x |
a |
x |
x |
x |
x |
- |
- |
- |
a |
a |
a |
x |
- |
- |
Group 2 |
|
|
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|
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|
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|
|
Levallorphan |
x |
o |
o |
- |
o |
a |
a |
a |
o |
a |
a |
x |
a |
a |
o |
- |
o |
x |
- |
o/a |
o/a |
a |
a |
a |
x |
x |
x |
Levo-methorphan (Dextro-methorphan) |
a |
a |
o/a |
x |
x |
a |
x |
a |
a |
a |
x |
x |
a |
a |
o |
- |
o |
o |
- |
- |
a |
x |
a |
x |
- |
o |
x |
Levorphanol (Dextrorphan) |
a |
a |
o/a |
a |
o |
a |
x |
a |
o/a |
a |
o/a |
- |
a |
a |
o |
- |
o |
a |
- |
- |
- |
x |
a |
a |
|
- |
a |
Phenomorphan |
a |
a |
a |
a |
a |
a |
a |
a |
o/a |
a |
a |
x |
a |
a |
o/a |
- |
a |
x |
a |
a |
a |
a |
a |
a |
x |
a |
a |
Racemethorphan |
a |
a |
a |
x |
x |
a |
a |
a |
a |
a |
x |
x |
a |
a |
o |
- |
o |
o |
- |
- |
x |
x |
a |
x |
o |
o |
o |
Racemorphan |
a |
a |
o |
a |
o |
a |
x |
a |
a |
a |
a |
- |
a |
a |
o |
- |
o |
x |
- |
- |
o/a |
x |
o/a |
a |
x |
a |
o |
Group 3a |
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|
Anileridine |
a |
o |
a |
x |
o/a |
a |
a |
a |
a |
a |
a |
x |
a |
a |
o |
a |
o |
o |
- |
x |
a |
a |
a |
a |
x |
o |
x |
Etoxeridine |
o |
o |
o |
x |
o |
o |
- |
x |
o |
o |
- |
- |
o |
a |
o |
o |
o |
- |
- |
- |
- |
o |
- |
o |
- |
- |
- |
x = crystals. a = amorphous. o = oil. o/a = oily amorphous. - = no precipitate.
Morpheridine |
a |
x |
a |
a |
x |
x |
a |
a |
x |
x |
x |
- |
x |
a |
o |
- |
x |
- |
- |
x |
a |
a |
a |
x |
- |
- |
- |
Pethideine |
x |
o |
o |
x |
o |
x |
x |
a |
a |
o |
- |
- |
o |
- |
o |
- |
o |
o |
- |
- |
- |
x |
x |
x |
- |
o |
- |
Properidine |
x |
o |
o |
x |
o |
x |
x |
a |
o |
o |
- |
x |
o |
x |
o |
- |
o |
o |
- |
- |
o |
a |
x |
x |
o |
o |
- |
Hydroxy-pethidine |
x |
x |
o |
- |
- |
x |
o |
a |
o |
o |
- |
- |
o |
a |
o |
- |
o |
o |
- |
- |
- |
a |
a |
x |
- |
- |
- |
Ketobemidone1 |
o |
o |
o |
- |
- |
o |
a |
a |
o/a |
a |
- |
- |
- |
a |
o |
- |
o |
- |
- |
- |
- |
a |
a |
o/a |
- |
- |
- |
Group 3 b |
|||||||||||||||||||||||||||
Alphameprodine |
x |
x |
o/a |
x |
o |
x |
x |
a |
o |
o/a |
x |
- |
a |
a |
o |
- |
o |
o |
- |
- |
x |
x |
x |
x |
- |
o |
- |
Alphaprodine |
a |
a |
o |
x |
o |
x |
a |
a |
a |
a |
- |
- |
a |
a |
o |
- |
o |
o |
- |
- |
x |
a |
x |
x |
- |
o |
- |
Betameprodine |
x |
x |
x |
x |
o |
x |
a |
a |
a |
a |
- |
- |
a |
o |
o |
- |
o |
o |
- |
- |
- |
a |
a |
x |
o |
o |
- |
Betaprodine |
x |
x |
x |
x |
o |
x |
a |
a |
a |
a |
- |
- |
a |
o |
x |
- |
o |
o |
- |
- |
- |
a |
x |
x |
o/a |
o |
- |
Trimeperidine |
a |
a |
a |
x |
o |
x |
- |
a |
o/a |
a |
- |
- |
a |
a |
o |
- |
o |
o |
- |
- |
- |
a |
a |
x |
- |
o |
- |
Group 3 c |
|||||||||||||||||||||||||||
Ethoheptazine |
o |
o |
o |
- |
- |
x |
a |
a |
o |
o |
- |
- |
o |
a |
o |
- |
o |
a |
- |
- |
- |
a |
a |
x |
- |
o |
- |
Proheptazine |
a |
a |
o |
a |
o |
a |
a |
a |
o/a |
a |
x |
x |
a |
a |
o |
- |
o |
o |
- |
- |
a |
a |
a |
a |
- |
o |
- |
Group 4 |
|||||||||||||||||||||||||||
Alpha-acetyl-methadol |
x |
x |
x |
x |
x |
x |
a |
x |
a |
x |
x |
x |
x |
a |
o |
x |
o/a |
o |
x |
x |
x |
a |
x |
x |
o |
o |
x |
Alphamethadol |
a |
x |
x |
a |
x |
a |
a |
a |
o |
a |
x |
- |
a |
a |
o |
- |
o |
o |
- |
x |
x |
a |
a |
x |
o |
o |
o |
Dipipanone |
a |
a |
a |
a |
o/a |
a |
x |
a |
o |
a |
a |
o |
a |
a |
o |
- |
a |
o |
- |
o/a |
a |
x |
a |
a |
a |
o |
o |
Isomethadone |
x |
x |
o |
a |
x |
x |
x |
a |
o |
a |
x |
x |
x |
a |
o |
- |
o |
o |
- |
- |
x |
x |
a |
a |
o |
o |
o |
Methadone |
x |
a |
x |
x |
x |
a |
o/a |
x |
a |
a |
o |
- |
x |
o/a |
x |
- |
x |
o |
- |
- |
a |
x |
a |
a |
x |
o |
x |
Normethadone |
o |
x |
x |
x |
o |
o/a |
a |
o/a |
o |
o |
x |
o |
x |
a |
- |
o |
o |
- |
- |
o/a |
a |
o/a |
o/a |
o/a |
o/a |
o |
o |
Phenadoxone |
a |
a |
a |
a |
o |
a |
a |
a |
a |
a |
a |
o |
a |
a |
x |
- |
o |
o |
o |
a |
x |
a |
x |
a |
o |
o |
o |
Group 5 |
|||||||||||||||||||||||||||
Dextro-moramide |
x |
x |
x |
a |
a |
a |
a |
a |
a |
a |
o/a |
- |
a |
a |
x |
a |
x |
x |
a |
- |
x |
a |
x |
a |
x |
a |
o |
Diethyl-thiambutene |
o |
o |
o |
x |
o |
x |
a |
a |
o |
o |
o |
x |
o |
a |
o |
- |
o |
o |
- |
o |
x |
a |
o |
o |
o |
o |
x |
Dimethyl-thiambutene |
o |
o |
o |
x |
o |
x |
a |
a |
o |
o |
x |
o |
x |
a |
o |
- |
o |
o |
- |
o |
x |
a |
x |
x |
o |
o |
x |
Dioxyphetyl butyrate |
x |
x |
x |
a |
x |
a |
a |
x |
o |
a |
x |
x |
a |
x |
o |
x |
o |
o |
o |
o |
a |
a |
x |
a |
o |
o |
x |
Ethylmethyl-thiambutene |
o |
o |
o |
x |
o |
a |
a |
a |
o |
a |
x |
a |
o |
a |
o |
- |
o |
o |
- |
o |
x |
a |
x |
x |
o |
o |
o |
Levo-moramide |
x |
x |
x |
a |
a |
a |
a |
a |
a |
a |
o/a |
- |
a |
a |
x |
a |
x |
x |
a |
- |
x |
a |
x |
a |
x |
a |
o |
Propoxy-phene |
a |
x |
a |
a |
o |
a |
a |
a |
o |
a |
o |
x |
a |
a |
x |
- |
x |
o |
- |
o |
a |
a |
a |
a |
o |
o |
o |
Race-moramide |
a |
x |
x |
a |
a |
a |
a |
a |
a |
a |
a |
a |
a |
a |
a |
- |
x |
x |
a |
x |
x |
x |
x |
a |
x |
x |
x |
Tolpronine |
o |
o |
o |
x |
o |
x |
o |
a |
o |
o |
- |
- |
o |
a |
x |
- |
x |
o |
- |
- |
- |
a |
a |
x |
o |
o |
- |
3570CT |
a |
a |
a |
a |
a |
a |
a |
a |
a |
a |
a |
o |
a |
a |
x |
o |
x |
o |
o |
a |
a |
a |
a |
a |
a |
a |
a |
3638CT |
a |
a |
a |
a |
o |
a |
a |
a |
a |
a |
a |
x |
a |
a |
a |
a |
a |
o |
o |
a |
a |
a |
a |
a |
o |
o |
a |
3633CT |
a |
a |
a |
a |
o |
a |
a |
a |
a |
a |
a |
x |
a |
a |
o |
x |
o |
o |
o |
o |
a |
a |
a |
a |
o |
o |
o |
3639CT |
a |
a |
a |
a |
o |
a |
a |
a |
a |
a |
a |
o |
a |
a |
o |
o |
o |
o |
o |
o |
a |
a |
a |
a |
o |
o |
o |
1 In 1% acetic acid
Alkaloid |
Reagent |
Type of crystal |
Sensitivity (µg) |
---|---|---|---|
Group 1 |
|
|
|
Acetyl-dihydro-codeine |
Gold bromide / hydrochloric acid |
Very small rosettes (o/n) |
0.25 |
|
Gold chloride |
Dense rosettes (o/n) |
0.25 |
|
Lead iodode |
ROSETTES OF LONG PLATES (O/n) |
0.5 |
|
Picric acid |
GELATINOUS ROSETTES (o/n) |
0.1 |
|
Platinum chloride |
Smudge rosettes |
1.0 |
|
Picrolonic acid |
BUNCHES OF SERRATED NEEDLES |
0.25 |
Desomorphine |
Mercuric chloride |
PLATES |
0.5 |
Methyl-desorphine |
Mercuric chloride |
Rosettes of plates (o/n) |
0.1 |
|
Picric acid |
Oily rosettes (o/n) |
0.25 |
|
Potassium bismuth iodide |
SMALL BLADES |
0.1 |
|
Potassium chromate |
Small oily crystals (o/n) |
0.1 |
|
Sodium phosphate |
LONG NEEDLES |
0.1 |
|
Di-sodium methyl arsonate |
Long needles |
1.0 |
Methyl-dihydro-morphine |
Gold bromide / hydrochloric acid |
Oily rosettes1 |
0.1 |
|
Picric acid |
Branching needles |
0.25 |
|
Platinum chloride |
Gelatinous rosettes |
0.25 |
|
Platinum iodide |
Bunches of fibres (o/n) |
0.5 |
|
Potassium bismuth iodide |
Small rosettes of plates |
0.025 |
|
Potassium cadmium iodide |
PLATES, SOME SERRATED |
0.25 |
|
Potassium mercury iodide |
FEATHERY ROSETTES |
0.1 |
|
Platinum bromide |
Bunches of oily needles (o/n) |
1.0 |
|
Styphnic acid |
Fans of oily needles (o/n) |
0.5 |
Metopon |
Potassium bismuth iodide |
VERY SMALL RODS |
0.1 |
|
Potassium tri-iodide (3) |
Rosettes of rods (o/n) |
0.5 |
|
Sodium carbonate |
Bundles of rods |
1.0 |
|
Picrolonic acid |
SERRATED NEEDLES |
0.5 |
|
Di-sodium methyl arsonate |
Bundles of rods |
1.0 |
Morphine-N-oxide |
Picric acid |
Dense golden rosettes (o/n) |
0.5 |
|
Platinum chloride |
SMALL OILY ROSETTES (O/n) |
0.5 |
|
Potassium tri-iodide (3) |
DENSE ROSETTES |
0.5 |
Myrophine |
Potassium tri-iodide (2) |
OILY NEEDLES |
0.25 |
|
Trinitro benzoic acid |
Smudge rosettes |
1.0 |
|
Picrolonic acid |
BUNCHES OF NEEDLES |
0.25 |
Nalorphine |
Potassium chromate |
FOUR-POINTED STARS |
0.5 |
|
Potassium mercury iodide |
SMUDGE ROSETTES OR FIBRES |
0.25 |
|
Potassium tri-iodide (1) |
Fuzzy rosettes of needles (o/n) |
0.25 |
|
Potassium tri-iodide (3) |
Dense rosettes of rods (o/n) |
0.25 |
Oxymorphone |
Gold bromide |
DENSE ROSETTES |
0.1 |
|
Gold bromide / hydrochloric acid |
Irregular crystals (2 days) |
1.0 |
|
Mercuric chloride |
FANS OF NEEDLES (O/n) |
0. 1 |
Pholcodine |
Platinum chloride |
FEATHERY ROSETTES |
0.25 |
|
Potassium bismuth iodide |
Dendrites (2 days) |
1.0 |
|
Styphnic acid |
ROSETTES OF PLATES (o/n) |
0.1 |
Thebacon |
Gold bromide |
Small curved needles |
0.025 |
|
Gold bromide/hydrochloric acid |
Small curved needles |
0.025, |
|
Gold chloride |
Small curved needles |
0.025, |
|
Mercuric chloride |
Rosettes of rods |
1.0 |
|
Picric acid |
Hedgehogs |
0.25 |
|
Potassium cadmium iodide |
FINE DENDRITES |
0.05 |
|
Potassium chromate |
Feathery needles |
1.0 |
|
Potassium mercury iodide |
FEATHERY ROSETTES |
0.025 |
|
Potassium tri-iodide (1) |
Branching needles |
0.025 |
|
Potassium tri-iodide (2) |
Rosettes of needles (2 days) |
1.0 |
|
Potassium tri-iodide (3) |
Branching needles (2 days) |
0.25 |
|
Sodium carbonate |
Rosettes of needles |
0.5 |
|
Di-sodium methyl arsonate |
Rosettes of rods |
1.0 |
Normorphine |
Gold bromide |
Rosettes (2 days) |
1.0 |
|
Gold bromide / hydrochloric acid |
Gelatinous rosettes |
0.25 |
|
Picric acid |
Branching needles (2 days) |
0.25 |
|
Potassium bismuth iodide |
ROSETTES OF PLATES |
0.1 |
See notes at end of table.
Alkaloid |
Reagent |
Type of crystal |
Sensitivity (µg) |
---|---|---|---|
Normorphine (contd.) |
Potassium cadmium iodide |
PLATES, OFTEN HEXAGONAL |
0.1 |
|
Potassium mercury iodide |
Plates, often hexagonal |
0.1 |
Norcodeine7 |
Gold bromide / hydrochloric acid |
Smudge rosettes |
0.5 |
|
Gold chloride |
Needles |
0.25 |
|
Potassium cadmium iodide |
Bunches of irregular needles |
0.05 |
|
Potassium chromate |
NEEDLES |
0.25 |
|
Potassium iodide |
Needles (2 days) |
0.5 |
|
Potassium mercury iodide |
Bunches of irregular needles |
0.05 |
|
Potassium tri-iodide (2) |
Needles (2 days) |
0.5 |
|
Zinc chloride |
NEEDLES |
0.1 |
|
Ammonium thiocyanate |
Fine rods |
0.25 |
Group 2 |
|
|
|
Levallorphan |
Gold bromide |
Irregular needles |
0.25 |
|
Potassium iodide |
NEEDLES AND PLATES (o/n) |
0.5 |
|
Sodium carbonate |
Dense rosettes (o/n) |
0.5 |
|
Di-sodium methyl arsonate |
Dense rosettes (o/n) |
0.5 |
|
Potassium cyanide |
Dense rosettes |
0.25 |
|
Ammonium thiocyanate |
BUNCHES OF RODS |
1.0 |
Levomethorphan |
Lead iodide |
BUNCHES OF SERRATED PLATES |
0.25 |
(Dextro-methorphan) |
Mercuric chloride |
Irregular rods |
0.25 |
|
Platinum chloride |
FEATHERY ROSETTES |
0.25 |
|
Potassium chromate |
Oily rosettes (o/n) |
1.0 |
|
Potassium iodide |
Curved plates (o/n) |
1.0 |
|
Platinum bromide |
Feathery rosettes |
1.0 |
|
Styphnic acid |
Dense rosettes |
0.25 |
|
Ammonium thiocyanate |
Curved plates |
1.0 |
Levorphanol (Dextrorphan) |
Platinum chloride |
MASSES OF SMALL IRREGULAR CRYSTALS |
0.25 |
|
Platinum bromide |
BUNCHES OF SMALL IRREGULAR PLATES |
0.25 |
Phenomorphan2 |
Potassium iodide |
Dense rosettes |
0.25 |
|
Sodium carbonate |
SMALL IRREGULAR PLATES |
0.1 |
|
Di-sodium methyl arsonate |
NEEDLES, SOME SERRATED |
0.1 |
Race-methorphan |
Lead iodide |
Dense rosettes (2 days) |
0.25 |
|
Mercuric chloride |
Irregular blades |
0.25 |
|
Potassium chromate |
Rosettes of plates |
1.0 |
|
Potassium iodide |
Plates |
1.0 |
|
Trinitrobenzoic acid |
ROSSETTES OF SMALL PLATES |
0.25 |
|
Platinum bromide |
Small plates |
0.25 |
|
Styphnic acid |
ROSETTES OF PLATES AND NEEDLES (O/n) |
0.25 |
Racemorphan |
Platinum chloride |
Dense rosettes (o/n) |
1.0 |
|
Sodium carbonate |
PLATES OR RODS IN BUNCHES |
0.25 |
|
Platinum bromide |
Rosettes of plates |
0.1 |
|
Disodium methyl arsonate |
ROSSETTES OF PRISMS |
0.25 |
Group 3 |
|
|
|
Alphameprodine |
Gold bromide |
Irregular needles (o/n) |
0.25 |
|
Gold bromide / hydrochloric acid |
Rosettes of plates and needles |
0.05 |
|
Lead iodide |
Dense rosettes |
0.1 |
|
Picric acid |
Minute curved needles |
0.025 |
|
Platinum chloride |
PLATES, OFTEN IN BUNCHES |
0 1 |
|
Potassium chromate |
Plates (o/n) |
1.0 |
|
Trinitrobenzoic acid |
Masses of small rods (o/n) |
0.25 |
|
Platinum bromide |
BUNCHES OF RODS OR PLATES |
0.1 |
|
Picrolonic acid |
Dense rosettes of plates (o/n) |
0.25 |
|
Styphnic acid |
Small irregular crystals |
0.25 |
Alphaprodine |
Lead iodide |
Dense rosettes |
0.25 |
|
Picric acid |
SMALL SERRATED PLATES, OFTEN IN BUNCHES |
0.025 |
|
Trinitrobenzoic acid |
Plates(o/n) |
1.0 |
|
Picrolonic acid |
Rosettes of plates (o/n) |
1 .0 |
|
Styphnic acid |
VERY SMALL CRYSTALS3 |
0.1 |
Anileridine |
Lead iodide |
BRANCHING RODS |
0.25 |
See notes at end of table.
Alkaloid |
Reagent |
Type of crystal |
Sensitivity (µg) |
---|---|---|---|
Anileridine (contd.) |
Potassium iodide |
LARGE PLATES AND SMALL NEEDLES FROM EDGE |
0.25 |
|
Zinc chloride |
Long needles (2 days) |
1.0 |
|
Di-sodium methyl arsonate |
Long plates (o/n) |
0.5 |
|
Ammonium thiocyanate |
Plates |
1.0 |
Beta-meprodine |
Gold bromide |
Serrated blades (o/n) |
0.025 |
|
Gold bromide / hydrochloric acid |
Rosettes of needles and plates |
0.25 |
|
Gold chloride |
Rosettes of needles |
0.25 |
|
Lead iodide |
SMALL BLADES, SOMETIMES IN ROSETTES |
0.1 |
|
Picric acid |
BUNCHES OF STOUT RODS |
0.1 |
|
Styphnic acid |
Small rosettes |
0.1 |
Betaprodine |
Gold bromide |
Branching rods and plates (o/n) |
0.025 |
|
Gold bromide / hydrochloric acid |
Serrated rods (o/n) |
0.25 |
|
Gold chloride |
Serrated plates and needles, sometimes in bunches |
0.05 |
|
Lead iodide |
ROSETTES OR BUNCHES OF IRREGULAR RODS |
0.1 |
|
Picric acid |
Irregular plates and rods |
0.25 |
|
Potassium tri-iodide (1) |
Plates (o/n) |
0.1 |
|
Picrolonic acid |
Dense rosettes (2 days) |
1.0 |
|
Styphnic acide |
PLATES, OFTEN IN ROSETTES |
0.1 |
Etoxeridine |
Lead iodide |
BURRS OF FINE NEEDLES |
1.0 |
|
Platinum iodide |
PLATES (o/n) |
1.0 |
Hydroxy-pethidine |
Gold bromide |
SMALL PLATES AND PRISMS |
0.1 |
|
Gold bromide / hydrochloric acid |
Plates, some serrated |
0.5 |
|
Picric acid |
Rosettes of plates |
1.0 |
|
Styphnic acid |
BLADES, SOMETIMES IN ROSETTES |
0.5 |
Ketobemidone4 |
Gold bromide |
Rods, some segmented |
0. 025 |
|
Gold bromide / hydrochloric acid |
Plates, some serrated |
0.05 |
|
Gold chloride |
Serrated needles and plates |
0.5 |
|
Potassium cadmium iodide |
Irregular crystals |
1.0 |
Morpheridine |
Gold bromide / hydrochloric acid |
Masses of very small crystals (o/n) |
0.25 |
|
Mercuric chloride |
Serrated plates, often in rosettes |
0.25 |
|
Picric acid |
Small rods and needles |
0.25 |
|
Potassium bismuth iodide |
SMALL ROSETTES AND FANS OF NEEDLES (o/n) |
0. 1 |
|
Potassium cadmium iodide |
PLATES, OFTEN IN BUNCHES (o/n) |
0.1 |
|
Potassium chromate |
Irregular crystals |
0.25 |
|
Potassium mercury iodide |
Small plates (o/n) |
0.25 |
|
Potassium tri-iodide (3) |
Rosettes of needles (o/n) |
1.0 |
|
Zinc chloride |
Plates |
1.0 |
|
Styphnic acid |
Minute crystals3 |
0.25 |
Pethide |
Gold bromide |
Plates, some serrated (o/n) |
0.25 |
|
Lead iodide |
Bunches of branching rods |
0.25 |
|
Picric acid |
FEATHERY ROSETTES |
0.1 |
|
Platinum chloride |
Plates and feathery rosettes (o/n) |
0.25 |
|
Platinum bromide |
Feathery rosettes (o/n) |
0.25 |
|
Picrolonic acid |
FEATHERY ROSETTES |
0.1 |
|
Styphnic acid |
Bunches of small plates |
0. 1 |
Propene |
Gold bromide |
Plates (2 days) |
1.0 |
|
Lead iodide |
MASSES OF BLADES, SOME SERRATED |
0.05 |
|
Picric acid |
Bunches of plates, often curved |
0.05 |
|
Platinum chloride |
Oily dendrites (o/n) |
0.25 |
|
Potassium iodide |
Long plates (2 days) |
1.0 |
|
Potassium permanganate |
PLATES, OFTEN LARGE AND SERRATED |
0. 1 |
|
Picrolonic acid |
Rosettes of plates (o/n) |
1.0 |
|
Styphnic acid |
Masses of transparent plates |
0.05 |
Trimepe |
Lead iodide |
ROSETTES OF NEEDLES |
0.25 |
Picric acid |
Dense rosettes |
1.0 | |
|
Styphnic acid |
FANS OR BUNCHES OF RODS, OFTEN SERRATED (o/n) |
0. 1 |
Ethohe |
Picric acid |
BUNCHES OF IRREGULAR RODS (o/n) |
0.5 |
|
Styphnic acid |
DENSE ROSETTES (o/n) |
0.25 |
Proher |
Potassium chromate |
BUNCHES OF PLATES |
1.0 |
|
Potassium iodide |
STOUT RODS OR PRISMS, OFTEN IN ROSETTES |
0.5 |
See notes at end of table.
Alkaloid |
Reagent |
Type of crystal |
Sensitivity (µg) |
---|---|---|---|
Group 4 |
|
|
|
Acetyl-methadol |
Gold bromide |
Branching rods (o/n) |
0.25 |
|
Gold bromide / hydrochloric acid |
Fans of irregular rods (o/n) |
0.25 |
|
Gold chloride |
Irregular rods |
0.25 |
|
Lead iodide |
Smudge rosettes |
0.05 |
|
Mercuric chloride |
Dense rosettes |
0.1 |
|
Picric acid |
Rosettes of blades |
0.05 |
|
Platinum iodide |
Dense rosettes |
0.25 |
|
Potassium cadmium iodide |
Hairlike rosettes (2 days) |
1.0 |
|
Potassium chromate |
SMALL ROSETTES OF PLATES |
0.1 |
|
Potassium iodide |
IRREGULAR RODS AND PLATES |
0.25 |
|
Potassium mercury iodide |
Bundles of small needles |
0.25 |
|
Potassium tri-iodide (2) |
Small rods or plates (o/n) |
1.0 |
|
Sodium phosphate |
Bunches of small needles (o/n) |
0.25 |
|
Zinc chloride |
Small oily needles |
0.25 |
|
Trinitrobenzoic acid |
Dense rosettes |
0.25 |
|
Picrolonic acid |
Dense rosettes (o/n) |
0.25 |
|
Styphnic acid |
Rosettes of small needles |
0.25 |
|
Ammonium thiocyanate |
Small rods and plates |
0.25 |
Methadol |
Gold bromide / hydrochloric acid |
Rosettes of plates (2 days) |
1.0 |
|
Gold chloride |
Irregular rods |
1.0 |
|
Mercuric chloride |
Dense rosettes (o/n) |
1.0 |
|
Potassium chromate |
FANS OF SMALL NEEDLES |
0.5 |
|
Zinc chloride |
RODS OR PLATES |
0.5 |
|
Trinitrobenzoic acid |
Dense rosettes |
1.0 |
|
Styphnic acid |
Dense rosettes of plates (o/n) |
0.1 |
Dipipanone |
Platinum chloride |
BUNCHES OF SERRATED BLADES |
0.1 |
|
Platinum bromide |
CURVING BLADES, MOSTLY SERRATED |
0.25 |
Isomethadone |
Gold bromide |
Bunches of plates |
0.25 |
|
Gold bromide / hydrochloric acid |
Oily needles and blades |
0.1 |
|
Mercuric chloride |
Rosettes of plates (2 days) |
1.0 |
|
Picric acid |
DENSE ROSETTES OF RODS |
0.25 |
|
Platinum chloride |
DENSE ROSETTES OF SMALL PLATES |
0.1 |
|
Potassium chromate |
Plates (o/n) |
0.25 |
|
Potassium iodide |
Bunches of prisms |
1.0 |
|
Potassium mercury iodide |
Plates or blades, some serrated |
0.25 |
|
Trinitrobenzoic acid |
Dense rosettes |
1.0 |
|
Platinum bromide |
Dense rosettes and rods |
0.1 |
Methadone |
Gold bromide |
Needles (o/n) |
0.25 |
|
Gold chloride |
Rods and plates (o/n) |
0.025 |
|
Lead iodide |
Dense rosettes of rods (o/n) |
0.25 |
|
Mercuric chloride |
ROSETTES OF BRANCHING RODS |
0.05 |
|
Platinum iodide |
Plates and needles (2 days) |
0.25 |
|
Potassium mercury iodide |
Needles |
0.025 |
|
Potassium tri-iodide (1) |
Splinters or needles |
0.025 |
|
Potassium tri-iodide (3) |
Splinters |
0.1 |
|
Platinum bromide |
BUNCHES OF PRISMS |
0.25 |
|
Di-sodium methyl arsonate |
Prisms (o/n) |
1.0 |
|
Ammonium thiocyanate |
Plates (o/n) |
1.0 |
Normethadone |
Gold bromide / hydrochloric acid |
SMALL PLATES, OFTEN CRUCIFORM |
0.1 |
|
Gold chloride |
Small blades and plates |
0.1 |
|
Lead iodide |
MASSES OF BLADES, SOME SERRATED |
0.1 |
|
Potassium chromate |
Prisms |
1.0 |
|
Potassium mercury iodide |
Rods and prisms (o/n) |
0.25 |
Phenadoxone |
Potassium tri-iodide (1) |
RODS AND PLATES (o/n) |
0.1 |
|
Trinitrobenzoic acid |
Smudge rosettes |
0.5 |
|
Picrolonic acid |
DENSE OILY ROSETTES |
0.1 |
Group 5 |
|
|
|
Diethyl-thlambutene |
Lead iodide |
Dense rosettes (o/n) |
0.25 |
|
Picric acid |
IRREGULAR BLADES (o/n) |
0.25 |
|
Potassium iodide |
ROSETTES OF PLATES |
0.5 |
See notes at end of table.
Alkaloid |
Reagent |
Type of crystal |
Sensitivity (µg) |
---|---|---|---|
Dimethylthiambutene |
Trinitrobenzoic acid |
Rosettes of needles (o/n) |
1.0 |
|
Ammonium thiocyanate |
Large rods (o/n) |
0.5 |
|
Lead iodide |
ROSETTES OF BRANCHING RODS |
0.1 |
|
Picric acid |
Small plates (o/n) |
0.5 |
|
Potassium chromate |
Prisms, usually rhomboidal |
0.5 |
|
Potassium mercury iodide |
LONG PLATES (o/n) |
0.1 |
|
Trinitrobenzoic acid |
Rosettes of branching needles |
0.25 |
|
Picrolonic acid |
Small feathery rosettes |
0.1 |
|
Styphnic acid |
Leaflike plates |
0.1 |
|
Ammonium thiocyanate |
Plates and needles |
1.0 |
Ethyl-methyl-thiambutene |
Lead iodide |
Oily rods (2 days) |
1.0 |
|
Potassium chromate |
TABLETS, USUALLY HEXAGONAL |
0.5 |
|
Trinitrobenzoic acid |
Rosettes of needles |
0.25 |
|
Picrolonic acid |
Rosettes of rods (2 days) |
0.25 |
|
Styphnic acid |
SERRATED NEEDLES |
0.25 |
Dextro-moramide |
Gold bromide |
Oily needles (o/n) |
1.0 |
(Levomoramide) |
Gold bromide / hydrochloric acid |
Oily needles (o/n) |
1.0 |
|
Gold chloride |
OILY NEEDLES, SOME SERRATED (o/n) |
0.25 |
|
Potassium tri-iodide (1) |
Oily needles |
1.0 |
|
Potassium tri-iodide (3) |
Blades |
1.0 |
|
Sodium carbonate |
Rosettes or masses of irregular crystals (o/n) |
0.25 |
|
Trinitrobenzoic acid |
Dense rosettes |
0.25 |
|
Picrolonic acid |
ROSETTES OF BRANCHING RODS, SOMETIMES DENSE |
0.25 |
|
Di-sodium methyl arsonate |
Bunches of prisms |
0.25 |
Dioxaphetyl-butyrate |
Gold bromide |
Transparent plates and needles (o/n) |
0.025 |
|
Gold bromide / hydrochloric acid |
Small irregular rods and plates |
0.25 |
|
Gold chloride |
Bunches of splinters |
0.25 |
|
Mercuric chloride |
Rosettes of needles |
1.0 |
|
Platinum iodide |
Small plates |
1.0 |
|
Potassium chromate |
FANS OF FINE NEEDLES |
0.5 |
|
Potassium iodide |
Plates |
0.5 |
|
Potassium permanganate |
Hairlike needles |
0.5 |
|
Potassium tri-iodide (2) |
Plates (2 days) |
0.25 |
|
Picrolonic acid |
Masses of needles, often curved |
0.25 |
|
Ammonium thiocyanate |
FINE DENDRITES |
0.25 |
Propoxyphene |
Gold bromide / hydrochloric acid |
CURVING BLADES (o/n) |
0.25 |
|
Potassium iodide |
Irregular crystals |
1.0 |
|
Potassium tri-iodide (1) |
SMALL PLATES IN FERNLIKE PATTERNS |
0.025 |
|
Potassium tri-iodide (3) |
Small plates in fernlike patterns |
0.025 |
Racemoramide |
Gold bromide / hydrochloric acid |
Branching needles (2 days) |
1.0 |
|
Gold chloride |
OILY NEEDLES, SOME SERRATED (o/n) |
0.1 |
|
Potassium tri-iodide (3)5 |
Plates and needles, often in rosettes |
1.0 |
|
Sodium carbonate |
Rosettes or masses of irregular crystals (o/n) 6 |
0.25 |
|
Trinitrobenzoic acid |
Dense rosettes |
0.25 |
|
Picrolonic acid |
ROSETTES OF BRANCHING RODS, SOMETIMES DENSE |
0.1 |
|
Di-sodium methyl arsonate |
Dense rosettes |
0.25 |
|
Potassium cyanide |
Irregular dense rosettes |
1.0 |
|
Ammonium thiocyanate |
LARGE PLATES |
1.0 |
Tolpronine |
Lead iodide |
Very small rosettes |
0.5 |
|
Picric acid |
ROSETTES OF FINE NEEDLES OR TABLES, SOMETIMES HEXAGONAL |
0.1 |
|
Potassium tri-iodide (1) |
PLATES, USUALLY RECTANGULAR |
0.1 |
|
Potassium tri-iodide (3) |
Rhomboids |
0.025 |
|
Styphnic acid |
Hedgehogs |
0.05 |
3570CT7 |
Potassium tri-iodide (1) |
SMALL PLATES (2 days) |
0.5 |
|
Potassium tri-iodide (3) |
SMALL PLATES (o/n) |
0.25 |
3638CT |
Potassium iodide |
DENSE ROSETTES (o/n) |
0.5 |
3633CT |
Potassium iodide |
ROSETTES OF RODS (o/n) |
0.5 |
|
Potassium tri-iodide (2) |
ROSETTES OF RODS (o/n) |
1.0 |
3639CT |
No crystals were obtained |
|
|
O/N (overnight). Crystals do not usually form till the following day.
1Crystals not stable.
2Saturated solution (about 1 in 400).
3Best seen under polarised light.
4In phosphoric acid.
5Excess alkaloid.
6 Sometimes bunches of prisms.
7Saturated solution (about 1 in 200).
Alkaloid |
Formaldehyde (Marquis) |
in μg |
Ammonium vanadate (Mandelin) |
in μg |
Ammonium molybdate (Frohde) |
in μg |
---|---|---|---|---|---|---|
Group 1 a |
|
|
|
|
|
|
Desmorphine |
Purple |
0.1 |
Grey-purple |
1.0 |
Deep violet - green - blue - yellow |
0.1 |
Methyl-desorphine |
Purple |
0.1 |
Brown |
0.25 |
Black-violet - greenish-brown |
0.1 |
Methyl-dihydro-morphine |
Purple |
0.1 |
Grey-purple - yellow |
0.5 |
Violet-blue - green |
0.1 |
Metopon |
Purple |
0.5 |
Dull violet |
0.25 |
Black-violet - blue-green |
0.1 |
Morphine-N-oxide |
Purple |
0.25 |
Dull purple - brown |
0.1 |
Deep violet - blue - green |
0.25 |
Nalorphine |
Purple |
0.25 |
- |
|
Deep blue - green |
0.25 |
Normorphine |
Purple |
0.1 |
Grey - green |
0.5 |
Purple - blue |
0.1 |
Oxymorphone |
Purple |
0.5 |
Brown |
1.0 |
Bright blue - green |
0.25 |
Group 1 b |
|
|
|
|
|
|
Acethyl-dihydro-codeine |
Purple |
0.25 |
- |
|
Green - blue |
0.25 |
Myrophine |
Red-purple |
0.25 |
- |
|
Blue-violet |
0.25 |
Norcodeine |
Purple |
0.1 |
- |
|
Blue-green - blue - green |
0.1 |
Pholcodeine |
Purple |
0.25 |
- |
|
Green - blue |
0.25 |
Thebacon |
Purple |
0.25 |
- |
|
Green - blue |
0.25 |
Group 2 |
|
|
|
|
|
|
Levallorphan |
- |
|
- |
|
Blue-green |
0.25 |
Levo-methorphan (Dextro-methorphan) |
- |
|
- |
|
Blue-green |
0.25 |
Levorphanol (Dextrophan) |
- |
|
- |
|
Blue-green |
0.25 |
Phenomorphan |
- |
|
- |
|
Blue-green |
0.25 |
Race-methorphan |
- |
|
- |
|
Blue-green |
0.25 |
Racemorphan |
- |
|
- |
|
Blue-green |
0.25 |
Group 3a |
|
|
|
|
|
|
Anileridine |
Dull orange |
1.0 |
- |
|
- |
|
Etoxeridine |
Dull orange |
1.0 |
- |
|
- |
|
Morpheridine |
Dull orange |
1.0 |
- |
|
- |
|
Pethidine |
Dull orange |
1.0 |
- |
|
- |
|
Properidine |
Dull orange |
1.0 |
- |
|
- |
|
Hydroxy-pethidine |
Dull orange |
1.0 |
Dull green |
0.5 |
Bright blue, fading |
0.25 |
Ketobemidone |
Dull orange |
1.0 |
Blue-green |
0.5 |
Bright blue, fading |
0.25 |
Group 3b |
|
|
|
|
|
|
Alpha-meprodine |
Brownish-red |
0.5 |
Blue-grey |
0.5 |
Blue-grey - green with blue rim |
0.5 |
Alphaprodine |
Brownish-red |
0.5 |
Blue-grey |
0.5 |
Blue-grey - green with blue rim |
0.5 |
Beta-meprodine |
Red-purple |
0.5 |
Blue-grey |
0.5 |
Blue-grey - green with blue rim |
0.5 |
Betaprodine |
Red-purple |
0.5 |
Blue-grey |
0.5 |
Blue-grey - green with blue rim |
0.5 |
Trimeperidine |
Red-purple |
0.25 |
- |
|
- |
|
Group 3c |
|
|
|
|
|
|
Ethoheptazine |
Dull orange |
0.5 |
- |
|
- |
|
Proheptazine |
Dull purple |
0.5 |
Grey-purple, fading |
0.25 |
Blue-grey - green |
0.25 |
Group 4 |
|
|
|
|
|
|
Alpha-acetyl-methadol |
Purple-brown - grey-green |
0.25 |
Grey-green |
0.25 |
Brown-purple-green |
0.25 |
Alphamethadol |
Purple-brown - grey-green |
0.25 |
Grey-green |
0.25 |
Brown-purple-green |
0.25 |
Dipipanone |
- |
|
Deep green-blue |
0.25 |
- |
|
Isomethadone |
- |
|
Brown-purple - violet-blue |
0.1 |
- |
|
Methadone |
- |
|
Faint green-blue |
0.5 |
- |
|
Normethadone |
- |
|
Yellow-green |
1.0 |
- |
|
Phenadoxone |
- |
|
Deep green-blue |
0.25 |
- |
|
Group 5 |
|
|
|
|
| |
Dextro-moramide |
- |
|
- |
|
- |
|
Diethyl-thiambutene |
Purple-brown |
0.1 |
Green - green-blue |
0.1 |
Orange-brown - pale green |
0.1 |
Dimethyl-thiambutene |
Purple-brown |
0.1 |
Green - green-blue |
0.1 |
Orange-brown - pale green |
0.1 |
Dioxaphteyl-thiambutene |
- |
|
- |
|
- |
|
Ethylmethyl-thiambutene |
Purple-brown |
0.1 |
Green - green-blue |
0.1 |
Orange-brown - pale green |
0.1 |
Propxyphene |
Black-violet - dull green |
0.5 |
Grey |
0.5 |
Black-green |
0.5 |
Racemoramide |
- |
|
- |
|
- |
|
Tolpronine |
Red |
0.5 |
Green-grey - grey-violet |
0.5 |
Grey-blue - green |
0.5 |
3570CT |
Yellow |
0.1 |
Yellow |
0.1 |
Yellow |
0.1 |
3638CT |
Yellow |
0.1 |
Yellow |
0.1 |
Yellow |
0.1 |
3633CT |
Yellow |
0.1 |
Yellow |
0.1 |
Yellow |
0.1 |
3639CT |
Yellow |
0.1 |
Yellow |
0.1 |
Yellow |
0.1 |
Alkaloid |
Selenious acid (Mecke) |
in μg |
Sodium tungstate (Reichard) |
in μg |
Vitalis test |
in μg |
---|---|---|---|---|---|---|
Group 1 a |
|
|
|
|
|
|
Desomorphine |
Black-violet - deep-green |
0.1 |
Grey |
0.25 |
Yellow / yellow / orange |
0.5 |
Methyl-desorphine |
Greenish-brown |
0.25 |
Deep purple |
0.25 |
Yellow / yellow / orange |
0.25 |
Methyl-dihydro-morphine |
Green |
0.25 |
Grey |
1.0 |
Yellow / yellow / orange |
1.0 |
Metopon |
Yellow-brown |
0.5 |
- |
|
Yellow / yellow / orange |
0.25 |
Morphine-N-oxide |
Green |
0.25 |
Grey-purple |
0.5 |
Yellow / yellow / orange |
0.5 |
Nalorphine |
Brown |
0.25 |
Black-purple |
0.5 |
Yellow / yellow / orange |
0.5 |
Normorphine |
Green |
0.25 |
Grey |
1.0 |
Yellow / yellow / orange |
0.25 |
Oxymorphine |
Yellow |
1.0 |
Deep violet |
1.0 |
Yellow / yellow / orange |
0.5 |
Group 1 b |
|
|
|
|
|
|
Acethyl-dihydro-codeine |
Green |
0.5 |
- |
|
Faint yellow / - / pale orange |
1.0 |
Myrophine |
Greenish-brown |
1.0 |
Faint purple |
1.0 |
Yellow / yellow / orange |
1.0 |
Norcodeine |
Green |
0.1 |
Grey |
0.5 |
Yellow / yellow / orange |
0.5 |
Pholcodeine |
Grey-green |
1.0 |
- |
|
Faint yellow / - / pale orange |
1.0 |
Thebacon |
Green |
0.5 |
- |
|
Faint yellow / - / pale orange |
1.0 |
Group 2 |
|
|
|
|
|
|
Levallorphan |
Yellow-brown |
0.5 |
Purple |
0.25 |
Yellow / yellow / orange |
0.25 |
Levo-methorphan (Dextro-methorphan) |
Yellow-brown |
0.5 |
Faint brown |
1.0 |
- |
|
Levorphanol (Dextrophan) |
Yellow-brown |
0.5 |
Purple |
0.25 |
Yellow / yellow / orange |
0.25 |
Phenomorphan |
Yellow-brown |
0.5 |
Purple |
0.25 |
Yellow / yellow / orange |
0.25 |
Racemethorphan |
Yellow-brown |
0.5 |
- |
|
Yellow / yellow / orange |
0.25 |
Racemorphan |
Yellow-brown |
0.5 |
Purple |
0.25 |
Yellow / yellow / orange |
0.25 |
Group 3a |
|
|
|
|
|
|
Anileridine |
- |
|
- |
|
/ pale yellow / light brown |
1.0 |
Etoxeridine |
- |
|
- |
|
- |
|
Morpheridine |
- |
|
- |
|
- |
|
Pethidine |
- |
|
- |
|
- |
|
Properidine |
- |
|
- |
|
- |
|
Hydroxypethidine |
Grey-blue - brown |
0.5 |
Reddish-purple |
0.5 |
--/--/ yellow |
0.25 |
Ketobemidone |
Blue-green |
0.25 |
Reddish-purple |
0.5 |
--/--/ yellow |
0.25 |
Group 3b |
|
|
|
|
|
|
Alphameprodine |
Orange-brown |
1.0 |
- |
|
- |
|
Alphaprdine |
Orange-brown |
1.0 |
- |
|
- |
|
Betameprodine |
Orange-brown |
1.0 |
- |
|
- |
|
Betaprodine |
Orange-brown |
1.0 |
- |
|
- |
|
Trimeperidine |
Yellow |
1.0 |
- |
|
- |
|
Group 3c |
|
|
|
|
|
|
Ethoheptazine |
- |
|
- |
|
- |
|
Proheptazine |
Yellow-brown - orange |
0.5 |
Yellow-brown - green-grey |
1.0 |
- |
|
Group 4 |
|
|
|
|
|
|
Alpha-acetyl-methadol |
Purple-brown - brown |
0.25 |
Faint green-grey |
1.0 |
- |
|
Alphamethadol |
Purple-brown - brown |
0.25 |
Faint green-grey |
1.0 |
- |
|
Dipipanone |
Light brown |
0.5 |
- |
|
- |
|
Isomethadone |
- |
|
-
|
- |
||
Methadone |
- |
|
-
|
- |
||
Normethadone |
- |
|
-
|
- |
||
Phenadoxone |
- |
|
-
|
- |
||
Group 5 |
|
|
|
|
|
|
Dextro-moramide |
- |
|
- |
|
- |
|
Diethyl-thiambutene |
Violet-blue |
0.1 |
Orange |
0.25 |
Red - green / brown / brown |
0.5 |
Dimethyl-thiambutene |
Violet-blue |
0.1 |
Orange |
0.25 |
Red - green / brown / brown |
0.5 |
Dioxaphteyl-thiambutene |
- |
|
- |
|
- |
|
Ethylmethyl-thiambutene |
Violet-blue |
0.1 |
Orange |
0.25 |
Red - green / brown / brown |
0.5 |
Levomoramide |
- |
|
- |
|
- |
|
Propxyphene |
Faint brown |
0.5 |
Grey |
1.0 |
- |
|
Racemoramide |
- |
|
- |
|
- |
|
Tolpronine |
Green |
0.5 |
Grey - grey-violet |
1.0 |
- |
|
3570CT |
Yellow |
0.1 |
Yellow |
0.1 |
Yellow /--/-- |
0.5 |
3638CT |
Yellow |
0.1 |
Yellow |
0.1 |
Yellow /--/-- |
0.5 |
3633CT |
Yellow |
0.1 |
Yellow |
0.1 |
Yellow /--/-- |
0.5 |
3639CT |
Yellow |
0.1 |
Yellow |
0.1 |
Yellow /--/-- |
0.5 |
Several crystal tests may be used to identify the different members of the group. The bunches of small irregular plates which levorphanol gives with platinum bromide do not differ greatly in appearance from the rosettes given by racemorphan. Both levomethorphan and racemethorphan give crystals with styphnic acid, the former dense rosettes, the latter rosettes of plates and needles.
Neither crystal nor colour tests serve to distinguish levorphanol and levomethorphan from their dextro isomers, although, as the table shows, the former may be used to distinguish between the racemic and the optically active forms. This fact affords a simple method of differentiating between (+) and ( - ) isomers (Clarke, [24] ). A drop of a solution of one known isomer is added to a drop of the test solution, followed by a drop of a suitable reagent (5 per cent sodium carbonate in the case of levorphanol and dextrophan, saturated trinitro-benzoic acid in the case of their methyl ethers). If the isomer added is the same as the unknown, the precipitate formed will be due to that isomer only, but if it is the enantiomorph, crystals typical of the racemate will be formed.
3. The pethidine group. With the Marquis reagent the reversed esters give varying shades of brownish or purplish red, while the other members give a dull orange. This latter test is not very delicate, and the colour may be missed altogether on the microgram scale. The sensitivity may be increased by adding the reagent to the residue heated to 100° C, but reagents containing sulphuric acid readily cause charring under these conditions, and cannot be used in this way with substances extracted from cadaveric material, which often char even in the cold. The other colour tests also serve chiefly to distinguish between esters and reversed esters, although the light blue colour given by the sulphuric acid-molybdate reagent with hydroxypethidine and ketobemidone helps to distinguish these two compounds, as does the reddish purple with the sulphuric acid-tungstate reagent.
Although most of these compounds form numerous crystalline derivatives, difficulty arises in two cases. With etoxeridine, the crystals formed with both lead iodide and platinum iodide form very slowly, and from concentrated solutions only. On occasions they may fail to appear at all, and thus cannot be regarded as providing a satisfactory test. With ketobemidone it was found impossible to obtain any crystals from solutions in dilute acids. Solutions in 90% phosphoric acid yielded excellent crystals with the gold halide reagents, but these are rather similar to those given by pethidine and hydroxypethidine under similar conditions. Differentiation may, however, be made by colour tests and by the fact that the latter substances readily form crystals from solutions in dilute acids.
The crystals formed by alphaprodine with styphnic acid are very small, and are best viewed under polarized light.
4. Methadone group. Only the alpha isomers of methadol and acetylmethadol were available. There is no single colour test by which members of this group may be identified, but several tests serve to distinguish methadol and acetylmethadol from methadone, normethadone, isomethadone, phenadoxone and dipipanone. The former give a purple-brown changing to grey-green with Marquis reagent, a brown-purple changing to green with the sulphuric acid-molybdate reagent, and a dull grey-green with the sulphuric acid-vanadate reagent. The ketone members of the group give colours with the last reagent only, normethadone giving a pale yellow-green, methadone, dipipanone and phenadoxone a green changing to blue, and isomethadone a transient brown-purple changing to violet-blue.
Numerous crystal tests serve to differentiate between members of the group. The crystals given by normethadone with the gold bromide/hydrochloric acid reagent are rather difficult to see, as they are usually mixed with amorphous material.
Alphamethadol and alpha-acetylmethadol may be distinguished from one another by the crystals they give with potassium chromate, the latter giving small rosettes of plates and the former rosettes and burrs of fine needles.
5. Miscellaneous group. The dialkylthiambutenes give brilliant colours with all the reagents used, the colour change with fuming nitric acid being particularly distinctive. In addition to the tests shown in table 4, these compounds give a red colour turning to green with the paraformaldehyde/ phosphoric acid reagent introduced for the detection of solanaine (Clarke, [18] ). The various members of the group may be distinguished from one another by crystal tests.
Both colour and crystal tests are available for the identification of propoxyphene and tolpronine. In the case of dioxyphetyl butyrate and moramide, however, no colour tests could be found, although there are several good crystal tests. The three isomers of the latter compound may be differentiated by the method described above for the N-methyl-morphinans, using a 5% solution of ammonium thiocyanate. Racemoramide gives large plates with this reagent, while the optically active forms give only oils. The latter are distinguished from one another by cross testing with a solution of one known enantiomorph. As the test is not particularly sensitive, concentrations should be in the range of 5%-1%.
The benzodioxans (Jacob, Blozovski, & Echinard-Garin, [25] ) give a bright yellow colour with all the sulphuric acid reagents. In this they resemble the benzhydryl ether derivatives (Clarke, [20] ). They form few crystalline derivatives, however, and differentiation between members of this group is not easy if only microgram quantities are available.
All the tests described in this paper were carried out with microgram quantities of the pure subtance. The sensitivities given refer to the actual quantity of the compound that may be detected in that particular test.
Crystal and colour tests are described for 51 analgesic drugs.
Examples of crystals obtaine dwith the micro-crystalline tests (continued)
(Unless otherwise indicated, the quantities shown are dissolved in 100 ml of water)
Gold bromide : 5 g gold chloride + 5 g sodium bromide.
Gold bromide / hydrochloric acid : 5 g gold chloride + 5 g sodium bromide in 100 ml concentrated hydrochloric acid.
Gold chloride : 5 g.
Lead iodide : Dissolve 30 g potassium acetate in 100 ml of water, adjust to pH6 with acetic acid, and saturate with lead iodide.
Mercuric chloride : 5 g.
Picric acid : 5 g.
Platinum chloride : 5 g.
Platinum iodide : 5 g platinum chloride + 25 g sodium iodide.
Potassium bismuth iodide : 5 g bismuth subnitrate + 25 g potassium iodide in 100 ml of 2% sulphuric acid.
Potassium cadmium iodide : 1 g cadmium iodide + 2 g potassium iodide.
Potassium chromate : 5 g.
Potassium iodide : 5 g.
Potassium mercury iodide : 1.5 g mercuric iodide + 5 g potassium iodide.
Potassium permanganate : 2 g potassium permanganate + 5 drops syrupy phosphoric acid.
Potassium tri-iodide (1) : 2 g iodine + 4 g potassium iodide.
Potassium tri-iodide (2) : 0.1 g iodine + 0.2 g potassium iodide.
Potassium tri-iodide (3) : 1 g iodine + 50 g potassium iodide.
Sodium carbonate : 5 g.
Sodium phosphate : 5 g Na 2HPO 4.
Zinc chloride : 5 g.
Trinitrobenzoic acid : Saturated solution.
Platinum bromide : 5 g platinum chloride + 10 g sodium bromide.
Picrolonic acid : Saturated solution.
Styphnic acid : 5 g.
Di-sodium methyl arsonate : 5 g.
Potassium cyanide : 5 g.
Ammonium thiocyanate : 5 g.
My thanks are due to Dr O. J. Braenden, Dr N. B. Eddy, Dr C. C. Fulton, Dr H. Isbell, Dr J. Jacob, Professor D. K. de Jongh, Dr D. Kharkevitch, Dr J. Marks, Mr P. Peterson, Dr J. M. Robins, Dr O. Schnider and Mr T. D. Whittet for help in obtaining material. I acknowledge most gratefully gifts of drugs from Messrs Allen & Hanbury, Ltd. ; British Drug Houses Ltd.; Burroughs Wellcome & Co.; Carlo Erba S.p.A.; Ciba (Basle) Ltd.; The Distillers Co., Ltd.; Farbwerke Hoechst AG.; Glaxo Laboratories, Ltd.; Laboratoire de recherches biologiques Laborec.; Eli Lilly & Co., Ltd.; H. Lundbeck & Co.; J. F. Macfarlan & Co., Ltd.; Merck Sharp & Dohme International; Mining and Chemical Products, Ltd.; Roche Products, Ltd.; S. A. Produits Bios; Sigurta Farmacutici; T. & H. Smith, Ltd.; Sojuzchimexport; and J. Wyeth & Brother, Ltd. I am also greatly indebted to Mr R. F. S. Creed and Mr H. Burgess for taking the photographs, and to Mrs Ann Williams for technical assistance.
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