Several common production schemes are used to obtain heroin, involving certain acetylation processes, the use of different solvents and equipment, and different initial salt forms of morphine. Depending on this, the appearance of the substance and the composition of the impurity components caused by the manufacturing process vary. For Afghan heroin manufactured from opium using acetic anhydride as an acetylating agent, such technological impurities are monoacetylmorphine, significant quantities of noscapine, less frequently morphine and acetylcodeine.
Heroin arriving on the market contains, as a rule, in large quantities (10-90%), in addition to technological, impurities of substances unrelated to the process of its manufacture and used as excipients. In expert studies, chloroquine phosphate, which is detected in heroin, was detected, as well as local, so-called "street" diluents: medicines (mainly in the form of crushed tablets) - difengidramin, analgin, acetylsalicylic acid, diazepam, ampicillin trihydrate, erythromycin, procaine, etc., as well as food products - starch, flour, sugar, sodium chloride, semolina, baby food, sodium bicarbonate (baking soda), etc.
The mass of heroin has no stable form of its own. Therefore, its individual definition is given either by indicating the quantity of the constituent substance, or by stating its individuality by origin, that is, by the particular place where the object in question was subjected to some kind of action (production, mixing, packaging).
Heroin arriving on the market contains, as a rule, in large quantities (10-90%), in addition to technological, impurities of substances unrelated to the process of its manufacture and used as excipients. In expert studies, chloroquine phosphate, which is detected in heroin, was detected, as well as local, so-called "street" diluents: medicines (mainly in the form of crushed tablets) - difengidramin, analgin, acetylsalicylic acid, diazepam, ampicillin trihydrate, erythromycin, procaine, etc., as well as food products - starch, flour, sugar, sodium chloride, semolina, baby food, sodium bicarbonate (baking soda), etc.
The mass of heroin has no stable form of its own. Therefore, its individual definition is given either by indicating the quantity of the constituent substance, or by stating its individuality by origin, that is, by the particular place where the object in question was subjected to some kind of action (production, mixing, packaging).
The examination of heroin begins with a microscopic examination of its physical properties - color, degree of crushing, and luminescence studies.
Microscopic examination makes it possible to establish the degree of homogeneity of the substance in terms of color and shape of crystals, to identify impurities in pharmaceutical tablets in the form of inclusions that vary in color and reflect the shape of parts of the tablets (smooth, flat or rounded surface; sometimes colored particles of the tablet shell). Even with sufficiently fine grinding of the mixture, sugar and sodium chloride (salt) crystals may be observed, mineral impurities such as sand are revealed.
Microscopic examination makes it possible to establish the degree of homogeneity of the substance in terms of color and shape of crystals, to identify impurities in pharmaceutical tablets in the form of inclusions that vary in color and reflect the shape of parts of the tablets (smooth, flat or rounded surface; sometimes colored particles of the tablet shell). Even with sufficiently fine grinding of the mixture, sugar and sodium chloride (salt) crystals may be observed, mineral impurities such as sand are revealed.
Afghan heroin has a citric-yellow or milky-yellow luminescence when examined under UV light at 366 nm. The same heroin in the form of surface lumps may have a dark purple luminescence, but a yellow luminescence is observed in the fracture. The method is not specific, nevertheless in the presence of an impurity, particles of a substance may be observed which sharply differ from heroin in luminescence color (for example, acetylsalicylic acid and chloroquine phosphate luminescent blue-lilac color, diphenhydramine-lilac-violet and others). The very presence of crystals of the substance, different in luminescence color, already indicates the heterogeneity of its composition.
Heroin in the form of the hydrochloride salt is readily soluble in water and chloroform, as well as in ethanol, and insoluble in diethyl ether. Therefore, if when dissolving it in chloroform an insoluble precipitate is found, easily soluble in water, this may indicate the presence of impurities of substances such as sugar and sodium chloride; if the particles of precipitate swell in water and become sodden, the presence of excipients such as semolina, starch, flour, baby food, etc. may be assumed.
Of course, with a multi-component composition of the substance the method is little informative, but it often helps to identify the presence of impurities and even partially differentiate them.
Of course, with a multi-component composition of the substance the method is little informative, but it often helps to identify the presence of impurities and even partially differentiate them.
In color tests, the presence of excipients changes the course of reactions in some cases. For example, many uncontrolled drugs form colored compounds with the Marky reagent (red-brown staining - amitriptyline; purple, changing to black-purple - erythromycin; red-purple - diclofenac sodium, etc.). Gradually increasing pink staining is produced by acetylsalicylic acid.
If diphenhydramine is present in the heroin, the addition of Markey's reagent causes an immediate bright yellow staining (diphenhydramine), which immediately changes to red-purple (heroin). If the diphenhydramine content is significant, the formation of brown staining interferes with the detection of heroin.
Certain organic substances, e.g. sugar, flour, are charred with sulfuric acid (a component of Markey's reagent). However, this does not produce a general red-violet coloring, but individual crystals and particles of red-brown color. When their amount does not exceed 10-15%, they have no significant effect on the reaction results for heroin.
If heroin contains an admixture of analgin, the test with nitric acid shows a momentary disappearing blue staining. The reaction then proceeds in the manner typical of heroin: yellow or yellow-orange staining, turning to green. In the presence of significant amounts of paracetamol, chloroquine phosphate, orange or orange-red staining appears, no transition to green is observed.
Thus, different drugs and organic substances can form in the rapid tests with heroin a staining similar to or different from that of heroin, which on the one hand can cause an error in the detection of heroin, but also suggests the presence of certain excipients, which further determines the choice of thin-layer chromatography (TLC) or gas-liquid chromatography (GLC).
If diphenhydramine is present in the heroin, the addition of Markey's reagent causes an immediate bright yellow staining (diphenhydramine), which immediately changes to red-purple (heroin). If the diphenhydramine content is significant, the formation of brown staining interferes with the detection of heroin.
Certain organic substances, e.g. sugar, flour, are charred with sulfuric acid (a component of Markey's reagent). However, this does not produce a general red-violet coloring, but individual crystals and particles of red-brown color. When their amount does not exceed 10-15%, they have no significant effect on the reaction results for heroin.
If heroin contains an admixture of analgin, the test with nitric acid shows a momentary disappearing blue staining. The reaction then proceeds in the manner typical of heroin: yellow or yellow-orange staining, turning to green. In the presence of significant amounts of paracetamol, chloroquine phosphate, orange or orange-red staining appears, no transition to green is observed.
Thus, different drugs and organic substances can form in the rapid tests with heroin a staining similar to or different from that of heroin, which on the one hand can cause an error in the detection of heroin, but also suggests the presence of certain excipients, which further determines the choice of thin-layer chromatography (TLC) or gas-liquid chromatography (GLC).
1. The sugar impurity. This impurity is separated, if possible, either mechanically under a microscope, or the substance is dissolved in chloroform and the solution is used for thin-layer chromatography and color tests, and the insoluble sediment is washed several times with chloroform and the exposure to sulfuric acid (charring).
2. Impurities of iodosorbent substances. For their detection a part of the substance (also after washing with chloroform and heroin) is heated to boiling with water, cooled down and a few drops of 0.01 % iodine solution is added. The blue staining that appears indicates the presence of iodine sorbents. If they consist of starch, the particles of the substance dissolve when heated, forming an opalescent solution. In the presence of flour, for example, solubility is not observed; in the presence of cereal or baby food particles of the substance swell, become friable, but do not dissolve. Microscopic examination of prepared preparations (magnification >200 times) reveals starch grains of the respective species.
2. Impurities of iodosorbent substances. For their detection a part of the substance (also after washing with chloroform and heroin) is heated to boiling with water, cooled down and a few drops of 0.01 % iodine solution is added. The blue staining that appears indicates the presence of iodine sorbents. If they consist of starch, the particles of the substance dissolve when heated, forming an opalescent solution. In the presence of flour, for example, solubility is not observed; in the presence of cereal or baby food particles of the substance swell, become friable, but do not dissolve. Microscopic examination of prepared preparations (magnification >200 times) reveals starch grains of the respective species.
We use the following solvent systems for TLC of heroin:
- benzene - ethanol - diethylamine (9:1:1);
- chloroform - toluene - acetone - ethanol (30:10:5:5), in a chamber saturated with ammonia vapor;
- ethyl acetate - methanol - ammonia 25% (85:10:5) (o/o).
As a stationary phase, plates with a 0.25 mm silica gel layer ("Kieselgel 60 F254″, "Silufol UV254″, etc.) are used.
Detection: 1) UV-light; 2) Marky's reagent; 3) Dragendorf's reagent (Silufol plates are not suitable for UV-light because they contain starch as a binder).
To perform chromatography in the presence of impurities on the plate put 2-3 samples of the test substance and one sample of the corresponding "witnesses". After separation, the plate is evaluated in UV light with a wavelength of 254 and 366 nm, to mark the spots. The chromatogram reveals heroin, some technological impurities and spots of fillers identified by the Rf value of the corresponding "witness"[6].
Then the plate is treated with developer reagents. When treating with reagent Marky, spots of heroin, technological admixtures of monoacetylmorphine, morphine, acetylcodeine in the form of spots of red and blue-violet color; diphenhydramine in the form of yellow spot, which color changes to dark yellow and brown depending on its quantitative content. Acetylsalicylic acid is revealed by a pink stain that intensifies over time. Note that acetylsalicylic acid may be used as an impurity alone or included in tablets. Acetylsalicylic acid is also well detected as a violet stain by 5% iron oxide chloride solution. Pentalgin tablets contain codeine, which is detected by Markey's reagent as a blue-violet stain. When detecting codeine and evaluating this sign (technological or introduced), it is necessary to proceed from the overall composition of the substance and the presence of other components.
Other samples are treated with the appropriate reagents by a zone, shielding the rest of the plate with glass. When shown with iron oxide chloride solution, analgin is revealed as a violet stain whose coloring changes to reddish-brown and then turns pale.
Other samples are treated with the appropriate reagents by zone, shielding the rest of the plate with glass. The iron oxide solution reveals analgin as a purple stain, which changes to a reddish brown color and then becomes pale.
Caffeine is detectable on the chromatogram under UV light and can also be detected by the Moulinier modified Dragendorff reagent, followed by stain enhancement by treatment with a 17% sulfuric acid solution.
Phenobarbital could be detected in the chromatogram by drying the plate in a stream of hot air under UV-light at 254 or by treating the chromatogram with mercury-diphenylcarbazone reagent or by treating it with 1% cobalt nitrate solution in absolute ethanol and then with ammonia vapor.
Paracetamol on the chromatogram reveal concentrated nitric acid (yellow staining of varying intensity, depending on the amount) or a 10% solution of ferric oxide chloride in 1% hydrochloric acid (blue-violet coloration). In the presence of small amounts, paracetamol is only detectable in UV light.
Chloroquine phosphate is detected under UV light at 254 and 366 nm by intense blue-lilac luminescence and by potassium bichromate solution in sulfuric acid (1 drop of 1% potassium bichromate solution is added to 2 ml of concentrated sulfuric acid). Butadiene is also detected with the same reagent.
Further, if necessary, heroin and impurities are quantified by gas-liquid chromatography or other available methods.
- benzene - ethanol - diethylamine (9:1:1);
- chloroform - toluene - acetone - ethanol (30:10:5:5), in a chamber saturated with ammonia vapor;
- ethyl acetate - methanol - ammonia 25% (85:10:5) (o/o).
As a stationary phase, plates with a 0.25 mm silica gel layer ("Kieselgel 60 F254″, "Silufol UV254″, etc.) are used.
Detection: 1) UV-light; 2) Marky's reagent; 3) Dragendorf's reagent (Silufol plates are not suitable for UV-light because they contain starch as a binder).
To perform chromatography in the presence of impurities on the plate put 2-3 samples of the test substance and one sample of the corresponding "witnesses". After separation, the plate is evaluated in UV light with a wavelength of 254 and 366 nm, to mark the spots. The chromatogram reveals heroin, some technological impurities and spots of fillers identified by the Rf value of the corresponding "witness"[6].
Then the plate is treated with developer reagents. When treating with reagent Marky, spots of heroin, technological admixtures of monoacetylmorphine, morphine, acetylcodeine in the form of spots of red and blue-violet color; diphenhydramine in the form of yellow spot, which color changes to dark yellow and brown depending on its quantitative content. Acetylsalicylic acid is revealed by a pink stain that intensifies over time. Note that acetylsalicylic acid may be used as an impurity alone or included in tablets. Acetylsalicylic acid is also well detected as a violet stain by 5% iron oxide chloride solution. Pentalgin tablets contain codeine, which is detected by Markey's reagent as a blue-violet stain. When detecting codeine and evaluating this sign (technological or introduced), it is necessary to proceed from the overall composition of the substance and the presence of other components.
Other samples are treated with the appropriate reagents by a zone, shielding the rest of the plate with glass. When shown with iron oxide chloride solution, analgin is revealed as a violet stain whose coloring changes to reddish-brown and then turns pale.
Other samples are treated with the appropriate reagents by zone, shielding the rest of the plate with glass. The iron oxide solution reveals analgin as a purple stain, which changes to a reddish brown color and then becomes pale.
Caffeine is detectable on the chromatogram under UV light and can also be detected by the Moulinier modified Dragendorff reagent, followed by stain enhancement by treatment with a 17% sulfuric acid solution.
Phenobarbital could be detected in the chromatogram by drying the plate in a stream of hot air under UV-light at 254 or by treating the chromatogram with mercury-diphenylcarbazone reagent or by treating it with 1% cobalt nitrate solution in absolute ethanol and then with ammonia vapor.
Paracetamol on the chromatogram reveal concentrated nitric acid (yellow staining of varying intensity, depending on the amount) or a 10% solution of ferric oxide chloride in 1% hydrochloric acid (blue-violet coloration). In the presence of small amounts, paracetamol is only detectable in UV light.
Chloroquine phosphate is detected under UV light at 254 and 366 nm by intense blue-lilac luminescence and by potassium bichromate solution in sulfuric acid (1 drop of 1% potassium bichromate solution is added to 2 ml of concentrated sulfuric acid). Butadiene is also detected with the same reagent.
Further, if necessary, heroin and impurities are quantified by gas-liquid chromatography or other available methods.
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