Introduction
Results
Discussion
Acknowledgements
Author: E. G. C. Clarke
Pages: 17 to 20
Creation Date: 1961/01/01
Since the publication of a previous paper on the identification of analgesic drugs (Clarke, 1959 a), additional substances have been brought under international control, or recommended for such restriction. It is the purpose of this paper to describe tests for seventeen of these new compounds.
It must be realized that the ever-increasing number of alkaloidal substances available makes their identification progressively more difficult. Although crystal tests are excellent for final confirmation when the compound has already been tentatively identified, they do not lend themselves to the "pinpointing" of one unknown substance out of the hundreds now in use for one purpose or another. Colour tests are more useful for this purpose, but are in many cases not available. To overcome this difficulty use may be made of paper chromatography, the system used by the writer being that described by Curry & Powell (1954). It is not proposed to consider here the details of paper chromatography, for which the reader is referred to the excellent paper by Genest & Farmilo (1959); but it must be emphasized that Rf values are not strictly reproducible, and no attempt should be made to effect an identification on the Rf value alone. Paper chromatography does, however, serve a most useful purpose in narrowing the field for identification by crystal and colour tests. Should it be necessary, these tests may be carried out on material eluted from the paper chromatogram (Clarke, 1960 a; Clarke & Hawkins, 1960).
Table 1 gives the approved name for the compound, its chemical name and the Rf value on the Curry & Powell system. Table 2 shows the type of precipitate obtained when a micro-drop of a 1% solution of the compound is added to a similar drop of the reagent. Table 3 shows the type of crystal obtained, those most suitable for identification purposes being printed in capitals. Table 4 shows the results of various colour tests. The composition of the reagents and the technique for carrying out the tests are as described previously (Clarke & Williams, 1955; Clarke, 1959 a).
Phenazocine and dimenoxadol have been included in the tables, although tests for these substances have already been described (Clarke, 1959b; Clarke, 1960b). R.951 (1-(3-oxo-3-phenylpropyl)-4-phenylpiperidine-4-carboxylic acid ethyl ester) has also been included, because it appears to have Outstanding analgesic properties (janssen, Jageneau, Van Proosdij-Hartzema & de Jongh, 1958). This compound is the ketone corresponding to the secondary alcohol phenoperidine.
It will be noted that while this group of new analgesic drugs includes derivatives of morphine, morphinan and pethidine, it also shows the introduction of fresh types of compound.
Some of these substances are not easy to identify; for example, hydromorphinol gives colour reactions similar to those of morphine, but even from concentrated solution forms few precipitates, only one of which is crystalline. Diampromide and phenamprornide give no satisfactory colour reactions and few crystals. Levophenacylmorphan gives colour reactions that are not particularly characteristic; while the test with picrolonic acid is of little value, as the crystals form only from dilute solutions, and often fail to appear. Furethidine forms no crystals and gives only a single non-specific colour reaction. This substance is noteworthy on account of the number of precipitates which form as oily droplets.
My thanks are due to Dr. Nathan B. Eddy; Dr Harris Isbell; Dr. Paul Janssen; Dr. E. L. May; British Drug Housses Ltd.; Ciba (Basle) Ltd.; J. F. Macfarlan & Co. Ltd. and G. D. Searle & Co. Ltd. for supplying me with compounds used for this work. I am also greatly indebted to Miss Ann Cooper and Miss Sandra Gavin for technical assistance.
Approved name or INN |
Chemical designation |
Rf value |
Approved name or INN |
Chemical designation |
Rf value |
---|---|---|---|---|---|
Allylprodine
|
3-allyl-1-methyl-4-phenyl-4-propion-oxypiperidine
|
0.69 |
Levo-phenacylmorphan
|
(-)-3-hydroxy-N-phenacylmorphinan
|
0.77 |
Benzethidine
|
1-(2-benzyloxyethyl)-4-phenylpiperi-dine-4-carboxylic acid ethyl ester
|
0.82 |
Metazocine
|
2'hydroxy-2,5,9-trimethyl-6,7-benzomorphan
|
0.48 |
Clonitazene
|
2-(
para-chlorbenzyl)-1-diethylami-noethyl-5-nitrobenzimidazole
|
0.66 |
Norlevorphanol
|
(-)-3-hydroxymorphinan
|
0.58 |
Diampromide
|
N-[2-(N-methylphenethylamino) propyl] propionanilide
|
0.76 |
Phenampromide
|
N-(1-methyl-2-piperidinoethyl) propionanilide
|
0.68 |
Dimenoxadol
|
2-dimethylaminoethyl - 1-ethoxy-1,1- diphenylacetate
|
0.60 |
Phenazocine
|
(±) 2'-hydroxy-5,9-dimethyl-2-phenethyl-6,7-benzomorphan
|
0.80 |
Diphenoxylate
|
1-(3-cyano-3, 3-diphenylpropyl)-4-phenylpiperidine-4-carboxylic acid ethyl ester
|
0.90 |
l-Phenazocine
|
(-) 2h-ydroxy-5,9-dimethyl-2-phenethyl-6,7-benzomorphan
|
0.80 |
Etonitazene
|
1-diethylaminoethyl-2-
para-ethoxy-benzyl-5-nitrobenzimidazole
|
0.70 |
Phenoperidine
|
1-(3 - hydroxy - 3 - phenylpropyl)-4-phenylpiperidine-4-carboxylic acid ethyl ester
|
0.84 |
Furethidine
|
1-(2-tetrahydrofurfuryloxyethyl)-4-phenylpiperidine-4-carboxylic acid ethyl ester
|
0.64 |
Piminodine
|
4-phenyl-1-(3-phenylaminopropyl)-piperidine-4-carboxylic acid ethyl ester
|
0.72 |
Hydromorphinol
|
14-hydroxydihydromorphine
|
0.11 |
R.951
|
1-(3-oxo-3-phenylpropyl)-4-phenylpiperidine-4-carboxylic acid ethyl ester
|
0.86 |
Alkaloid and reagent |
Type of crystal |
Sensitivity (μg) |
Alkaloid and reagent |
Type of crystal |
Sensitivity (μg) |
---|---|---|---|---|---|
Allylprodine
|
Hydromorphinol
|
||||
Lead iodide
|
Dense rosettes
|
0.1 |
Gold bromide/hydrochloric acid
|
VERY SMALL PLATES
|
1.0 |
Platinum chloride
|
Dense rosettes o/n
|
1.0 |
Levophenacylmorphan
|
||
Picric acid
|
SMALL PLATES
|
0.25 |
Picrolonic acid
|
Small oily needles
|
0.25
a
|
Trinitrobenzoic acid
|
Dense rosettes
|
1.0 |
Metazocine
|
||
Picrolonic acid
|
Rosettes of rods
|
0.1 |
Platinum chloride
|
Bunches of small plates
|
0.25 |
Styphnic acid
|
SMALL IRREGULAR PLATES
|
0.25 |
Sodium carbonate
|
DENSE ROSETTES OR PRISMS
|
0.25 |
Benzethidine
|
Trinitrobenzoic acid
|
Segmented plates
|
1.0 | ||
Gold chloride
|
SMALL PLATES o/n
|
0.1 |
Platinum bromide
|
Dense rosettes
|
1.0 |
Potassium iodide
|
Branching needles
|
1.0 |
Picrolonic acid.
|
CURVING NEEDLES
|
0.25 |
Potassium permanganate
|
FEATHERY ROSETTES o/n
|
0.1 |
Di-sodium methyl arsonate
|
Dense rosettes
|
1.0 |
Picrolonic acid
|
Smudge rosettes o/n
|
1.0 |
Potassium cyanide
|
Dense rosettes
|
1.0 |
Styphnic acid
|
Masses of blades o/n
|
0.25 |
Norlevorphanol
|
||
Clonitazene
|
Gold bromide
|
Rosettes of needles
|
0.25 | ||
Gold bromide/hydrochloric acid
|
Rosettes of curved needles
|
0.25 |
Gold bromide/hydrochloric acid
|
ROSETTES OF RODS
|
0.1 |
Mercuric chloride
|
Rosettes of rods
|
1.0 |
Gold chloride
|
Rosettes of rods
|
1.0 |
Potassium chromate
|
Bunches of blades
|
0.25 |
Mercuric chloride
|
Dense rosettes o/n
|
1.0 |
Potassium iodide
|
Bunches of plates
|
0.5 |
Picric acid
|
Dense rosettes o/n
|
1.0 |
Potassium tri-iodide (1)
|
SMALL PLATES OR NEEDLES o/n
|
0.25 |
Platinum chloride
|
IRREGULAR BLADES
|
0.5 |
Potassium tri-iodide (2)
|
Bunches of plates o/n
|
0.25 |
Platinum bromide
|
Rectangular plates
|
0.5 |
Zinc chloride
|
VERY SMALL ROSETTES
|
0.1 |
Phenampromide
|
||
Picrolonic acid
|
Small rosettes o/n
|
0.25 |
Gold bromide
|
SERRATED BLADES
|
0.25 |
Ammonium thiocyanate
|
Bunches of plates
|
0.25 |
Gold bromide/hydrochloric acid
|
PLATES OR PRISMS o/n
|
0.25 |
Diampromide
|
dl-Phenazocine
|
||||
Lead iodide
|
Dense rosettes and tablets o/n
|
1.0 |
Potassium iodide
|
ROSETTES OF OILY NEEDLES
|
1.0 |
Dimenoxadol
|
Potassium tri-iodide (2)
|
ROSETTES OF CURVING NEEDLES
|
1.0 | ||
Gold chloride
|
Bunches of needles o/n
|
1.0 |
Sodium carbonate
|
Bunches of prisms
|
1.0 |
Lead iodide
|
Rectangular plates
|
0.25 |
Sodium phosphate
|
Rosettes o/n
|
1.0 |
Platinum chloride
|
Small dense rosettes
|
0.25 |
Di-sodium methyl arsonate
|
Bunches of prisms
|
1.0 |
Trinitrobenzoic acid
|
Small rosettes
|
1.0 |
Potassium cyanide
|
Bunches of prisms
|
1.0 |
Platinum bromide
|
ROSETTES OF BRANCHING RODS
|
0.25 |
l-Phenazocine
|
||
Picrolonic acid
|
Small rosettes of rods
|
0.25 |
Sodium carbonate
|
FANS OF OILY NEEDLES o/n
|
1.0 |
Styphnic acid
|
BUNCHES OF IRREGULAR PLATES
|
0.25 |
Picrolonic acid
|
SHELL - LIKE CRYSTALS
|
1.0 |
Mercuric chloride
|
Rhomboids
|
1.0 |
Styphnic acid
|
Shell-like crystals
|
1.0 |
Diphenoxylate
|
Di-sodium methyl arsonate
|
Fans of oily needles o/n
|
1.0 | ||
Potassium iodide
|
SMUDGE ROSETTES
|
0.25 |
Potassium cyanide
|
Smudge rosettes o/n
|
1.0 |
Potassium tri-iodide (1)
|
Bunches of needles o/n
|
1.0 |
Phenoperidine
|
||
Potassium tri-iodide (2)
|
BUNCHES OF PLATES
|
0.25 |
Platinum chloride
|
Dense rosettes o/n
|
0.25 |
Ammonium thiocyanate
|
Branching needles o/n
|
0.5 |
Potassium chromate
|
Rosettes of rods
|
0.25 |
Etonitazene
|
Potassium iodide
|
ROSETTERS OF RODS
|
0.5 | ||
Gold bromide/hydrochloric acid
|
Curved oily needles o/n
|
0.25 |
Potassium permanganate
|
PLATES OR B LADES
|
0.1 |
Picric acid
|
Needles
|
1.0 |
Potassium tri-iodide (2)
|
Dense rosettes o/n
|
1.0 |
Potassium cadmium iodide
|
Rosettes or feathery crystals
|
0.25 |
Platinum bromide
|
Gelatinous or smudge rosettes o/n
|
0.25 |
Potassium chromate
|
BUNCHES OF RECTANGULAR PLATES
|
0.25 |
Piminodine
|
||
Potassium iodide
|
Needles or blades
|
1.0 |
Lead iodide
|
Masses of needles
|
0.5 |
Potassium tri-iodide (1)
|
Dense rosettes o/n
|
1.0 |
Picric acid
|
Curved branching needles
|
0.1 |
Potassium tri-iodide (2)
|
Bunches of plates or prisms
|
1.0 |
Platinum chloride
|
Sheaves of oily needles
|
1.0 |
Potassium tri-iodide (3)
|
Prisms or rosettes
|
1.0 |
Potassium chromate
|
BUNCHES OF BLADES
|
0.25 |
Picrolonic acid
|
Bunches of prisms
|
0.25 |
Potassium iodide
|
SMALL ROSETTES OF ELIDES
|
0.25 |
Ammonium thiocyanate
|
BUNCHES OF RODS OR PRISMS
|
0.25 |
Potassium tri-iodide (1)
|
Small irregular rosettes
|
1.0 |
Furethidine
|
Potassium tri-iodide (2)
|
Small irregular crystals
|
0.25 | ||
-
|
-
|
-
|
Potassium tri-iodide (3)
|
Small irregular crystals
|
1.0 |
Piminodine (contd.)
|
Lead iodide
|
Oily blades o/n
|
0.25 | ||
Platinum bromide
|
Masses of oily needles o/n
|
0.25 |
Platinum chloride
|
Curved needles
|
1.0 |
Styphnic acid
|
Branching needles o/n
|
1.0 |
Potassium chromate
|
Rosettes of needles
|
0.1 |
Ammonium thiocyanate
|
Large needles o/n
|
1.0 |
Potassium iodide
|
Very small needles
|
0.25 |
Trinitrobenzoic acid
|
Dense rosettes o/n
|
1.0 |
Potassium mercury iodide
|
Curved needles o/n
|
1.0 |
R. 951
|
Potassium permanganate
|
Small plates or needles
|
0.25 | ||
Gold bromide
|
Oily needles
|
1.0 |
Potassium tri-iodide (1)
|
Rosettes of needles
|
1.0 |
Gold bromide/hydrochloric
|
Potassium tri-iodide (2)
|
ROSETTES OF NEEDLES
|
0.25 | ||
acid
|
Oily needles o/n
|
1.0 |
Potassium tri-iodide (3)
|
Bunches of oily needles
|
1.0 |
Gold chloride
|
Oily needles o/n
|
0.25 |
Ammonium thiocyanate
|
BUNCHES OF PLATES OR NEEDLES
|
0.1 |
o/n (overnight = Crystals do not form until the following day.
a Crystals form from dilute solutions only.
Alkaloid |
Marquis |
Sensitivity (μg) |
Ammonium vanadate |
Sensitivity (μg) |
Ammonium molybdate |
Sensitivity (μg) |
---|---|---|---|---|---|---|
Allylprodine
|
Blue-black
|
0.1 |
Grey-green
|
1.0 |
Grey → green
|
1.0 |
Benzethidine
|
Orange
|
1.0 |
Orange-brown
|
1.0 |
Orange-brown
|
1.0 |
Clonitazene
|
-
|
-
|
-
|
-
|
Grey-blue
|
1.0 |
Diampromide
|
Orange
|
1.0 |
-
|
-
|
-
|
-
|
Dimenoxadol
|
Orange → greenish blue
|
0.1 |
Orange → brown → purple
|
0.1 |
Orange → brown → dull purple
|
0.1 |
Diphenoxylate
|
-
|
-
|
-
|
-
|
-
|
-
|
Etonitazene
|
Faint orange
|
1.0 |
-
|
-
|
Pale green
|
1.0 |
Furethidine
|
Faint orange
|
1.0 |
-
|
-
|
-
|
-
|
Hydromorphinol
|
Purple
|
0.1 |
Grey
|
0.1 |
Purple → blue → yellow
|
0.1 |
Levo-phenacylmorphan
|
Faint purple → grey → green
|
1.0 |
Grey-blue
|
1.0 |
Bright blue
|
0.5 |
Metazocine
|
Brown
|
1.0 |
Greenish-brown
|
1.0 |
Bright blue → green
|
1.0 |
Norlevorphanol
|
Olive
|
1.0 |
-
|
-
|
Blue → yellow-green
|
0.1 |
Phenampromide
|
-
|
-
|
-
|
-
|
-
|
-
|
dl-Phenazocine
|
Brown
|
1.0 |
Greenish-brown
|
1.0 |
Bright blue → green
|
1.0 |
l-Phenazocine
|
Brown
|
1.0 |
Greenish-brown
|
1.0 |
Bright blue → green
|
1.0 |
Phenoperidine
|
-
|
-
|
-
|
-
|
Faint grey-purple
|
1.0 |
Piminodine
|
-
|
-
|
-
|
-
|
-
|
-
|
R.951
|
-
|
-
|
-
|
-
|
-
|
-
|
Alkaloid |
Selenious acid |
Sensitivity (μg) |
Sodium tungstate |
Sensitivity (μg) |
Vitalis test |
Sensitivity (μg) |
---|---|---|---|---|---|---|
Allylprodine
|
Pale olive
|
1.0 |
Blue-grey
|
1.0 |
Yellow/yellow/grey → purple-brown
|
0.5 |
Benzethidine
|
Orange-brown
|
1.0 |
Faint grey
|
1.0 |
-/-/-
|
-
|
Clonitazene
|
-
|
-
|
-
|
-
|
Faint brown/faint brown/yellow-brown
|
1.0 |
Diampromide
|
-
|
-
|
-
|
-
|
-/-/-
|
-
|
Dimenoxadol
|
Orange
|
0.1 |
Orange → purple
|
0.1 |
-/-grey
|
1.0 |
Diphenoxylate
|
-
|
-
|
-
|
-
|
-/-/-
|
-
|
Etonitazene
|
Yellow
|
1.0 |
Yellow-brown
|
1.0 |
Light brown/lt. brown/yellow-brown
|
1.0 |
Furethidine
|
-
|
-
|
-
|
-
|
-/-/-
|
-
|
Hydromorphinol
|
Green
|
0.1 |
Grey-purple
|
0.1 |
Yellow/yellow/orange
|
0.5 |
Levo-phenacylmorphan
|
Pale yellow
|
1.0 |
Black-purple
|
0.25 |
Yellow/yellow/orange
|
0.25 |
Metazocine
|
Brown
|
1.0 |
Grey-purple
|
1.0 |
Yellow/yellow/orange
|
1.0 |
Norlevorphanol
|
Yellow-brown
|
1.0 |
Black-purple
|
0.5 |
Yellow/yellow/orange
|
1.0 |
Phenampromide
|
-
|
-
|
-
|
-
|
-/-/-
|
-
|
dl-Phenazocine
|
Brown
|
1.0 |
Black-purple
|
0.1 |
Yellow/yellow/orange
|
1.0 |
l-Phenazocine
|
Brown
|
1.0 |
Black-purple
|
0.1 |
Yellow/yellow/orange
|
1.0 |
Phenoperidine
|
Faint brown
|
1.0 |
-
|
-
|
-/-/faint orange
|
1.0 |
Piminodine
|
-
|
-
|
-
|
-
|
Bright orange/yellow/orange
|
0.5 |
R.951
|
-
|
-
|
-
|
-
|
-/-/faint orange
|
1.0 |
REFERENCES
CLARKE, E. G. C., Bull. Narcotics, XI, (1) 27 (1959 a).
CURRY, A. S. & POWELL, H., Nature, 173, 1143 (1954).
GENEST, K. & FARMILO, C. G., Bull. Narcotics, XI, (4) 20 (1959).
CLARKE, E. G. C., Nature, 188, 411 (1960 a).
CLARKE, E. G. C. & HAWKINS, A. E., J. Pharm. Pharmacol 12, 509 (1960).
CLARKE, E. G. C. & WILLIAMS, M., Bull. Narcotics, VII, (3-4), 33
CLARKE, E. G. C., Nature, 184, 451 (1959 b).
CLARKE, E. G. C., Bull. Narcotics, XII (1) 41 (1960 b).
JANSSEN, P. A. J., JAGENEAU, A. H., VAN PROOSDIJ-HARTZEMA, E. G. & DE JONGH, D. K., Act. Physiol. Pharmacol Needandica, 7, 373 (1958).