Introduction.
Phenyltetrahydroimidazothiazole (i.e., levamisole, dexamisole, ortetramisole) has been increasingly utilized as a cutting agent by South American illicit cocaine laboratories for the past eight years, and is now the most predominant adulterant in cocaine produced in Colombia. The salt form of illicit cocaine must be determined when possible for sentencing purposes; this is typically done via infrared spectroscopy. Two separation techniques for cocaine/phenyltetrahydroimidazothiazole mixtures are presented to common users or sellers. Mixtures of cocaine (hydrochloride and base) and phenyltetrahydroimidazothiazole (85:15, 70:30, and 50:50) were prepared and separated with liquid/liquid extraction and ion-pair chromatography. Recovered cocaine was subsequently analyzed via infrared spectroscopy, gas chromatography-flame ionization detection, and isotope ratio mass spectrometry. A qualitative reaction for the determination of sulfur in organic compounds will be described also.
Qualitative method for tetramisole sulfur.
You need:- Metallic sodium;
- Test tube (2 or more);
- Filter paper;
- Alcohol burner;
- Porcelain cup;
- Glass rod;
- Sodium nitroprusside/10% hydrochloric acid/acetic acid+ lead acetate.
Important: It is necessary to use safety glasses, protective clothing (chemical or medical gown), protective gloves; Experiment in a pull-out room or well-ventilated area!
Method:
Detection of tetramisole by fusing cocaine with metallic sodium. Sulfur from the tetramisole heterocycle is found in the cocaine product as follows: first, the sample is fused with metallic sodium, the released sulfur forms sulfide with sodium.
The sulfide ion is determined by conventional qualitative reactions. Several lumps of the analyzed cocaine, which is supposedly mixed with tetramisole, and a piece of metallic sodium with a shiny surface the size of half a pea are introduced into a dry test tube. Sodium should be stripped of oxides, squeezed out on filter paper from kerosene (in which it is stored). After, fusion is carried out. The tube is gently heated in a flame of an alcohol burner until red-hot and kept for 1-2 minutes. It is necessary for the sodium to melt with the cocaine sample because otherwise, sodium sulfide is not formed. Then the red-hot end of the test tube is dipped into a porcelain cup with 3 ml of distilled water. The tube will crack(be careful! If the sodium has not fully reacted, a flash may occur!). Pieces of melt are crushed with a glass rod and the colorless solution is poured into a test tube (if necessary, it is filtered through a small paper filter). If the organic substance is not completely destroyed, the liquid is brown or black. In this case, the fusion of the test substance with sodium is repeated.
Sodium nitroprusside solution 0.5 ml of 2% is added to the sample solution. An intense red-violet color appears, gradually turning into brown.
You can also experiment with a 10% hydrochloric acid solution, and a characteristic odor appears.
The third method is to add a few drops of acetic acid, then add 0.5 ml of a 2% solution of lead acetate. The liquid turns brown or black, sometimes a black precipitate appears. Sludge formation is accelerated by heating.
Qualitative reactions shown sulfur in the sample of cocaine, it means that sample contains tetramisole or another sulfur-organic substance.
Method:
Detection of tetramisole by fusing cocaine with metallic sodium. Sulfur from the tetramisole heterocycle is found in the cocaine product as follows: first, the sample is fused with metallic sodium, the released sulfur forms sulfide with sodium.
The sulfide ion is determined by conventional qualitative reactions. Several lumps of the analyzed cocaine, which is supposedly mixed with tetramisole, and a piece of metallic sodium with a shiny surface the size of half a pea are introduced into a dry test tube. Sodium should be stripped of oxides, squeezed out on filter paper from kerosene (in which it is stored). After, fusion is carried out. The tube is gently heated in a flame of an alcohol burner until red-hot and kept for 1-2 minutes. It is necessary for the sodium to melt with the cocaine sample because otherwise, sodium sulfide is not formed. Then the red-hot end of the test tube is dipped into a porcelain cup with 3 ml of distilled water. The tube will crack(be careful! If the sodium has not fully reacted, a flash may occur!). Pieces of melt are crushed with a glass rod and the colorless solution is poured into a test tube (if necessary, it is filtered through a small paper filter). If the organic substance is not completely destroyed, the liquid is brown or black. In this case, the fusion of the test substance with sodium is repeated.
Sodium nitroprusside solution 0.5 ml of 2% is added to the sample solution. An intense red-violet color appears, gradually turning into brown.
You can also experiment with a 10% hydrochloric acid solution, and a characteristic odor appears.
The third method is to add a few drops of acetic acid, then add 0.5 ml of a 2% solution of lead acetate. The liquid turns brown or black, sometimes a black precipitate appears. Sludge formation is accelerated by heating.
Qualitative reactions shown sulfur in the sample of cocaine, it means that sample contains tetramisole or another sulfur-organic substance.
Experiments.
Materials.
Celite 545 and all chemicals and solvents used were reagent grade or better and were obtained from Sigma-Aldrich. Cocaine hydrochloride (HCl) and tetramisole HCl were obtained from this laboratory’s reference materials collection. The glass chromatographic columns used for ion-pairsepa-rations were 260 mm× 22 mm i.d. with a stem length of 50 mm. Columns preparation: the celite 545 stationary phases was used without any pre-treatment; a column packed with a mixture of Celite545 and substances described below.
Liquid/liquid Separations.
Aqueous/organic solvent combinations were utilized in order to separate mixtures of cocaine HCl and tetramisole HCl (85:15, 70:30, 50:50). Each of the 50 mg cocaine HCl/tetramisole HCl mixtures (85:15, 70:30, 50:50) were converted to the base form by dissolving the mixture in boiling water and adding dilute ammonium hydroxide (NH4OH) until the solution was basic and precipitation occurred.
The mixture was allowed to cool, and the water was removed. The remaining base mixture was allowed to dry overnight. Ten 50 mg portions were combined with 5 ml of hexane in 10 separate 15 ml glassround-bottom centrifuge tubes (five test tubes per solvent). All samples were heated at 75 °C for approximately 5 min. Once the solutions were cooled, 5 ml of water were added to each test tube. The samples were shaken vigorously and centrifuged for 2 min. The solvent layer was removed and washed again with water. The washing process was repeated up to five times (Table 1). The washed solvent was evaporated to dryness and examined via FTIR and GC/FID.
Celite 545 and all chemicals and solvents used were reagent grade or better and were obtained from Sigma-Aldrich. Cocaine hydrochloride (HCl) and tetramisole HCl were obtained from this laboratory’s reference materials collection. The glass chromatographic columns used for ion-pairsepa-rations were 260 mm× 22 mm i.d. with a stem length of 50 mm. Columns preparation: the celite 545 stationary phases was used without any pre-treatment; a column packed with a mixture of Celite545 and substances described below.
Liquid/liquid Separations.
Aqueous/organic solvent combinations were utilized in order to separate mixtures of cocaine HCl and tetramisole HCl (85:15, 70:30, 50:50). Each of the 50 mg cocaine HCl/tetramisole HCl mixtures (85:15, 70:30, 50:50) were converted to the base form by dissolving the mixture in boiling water and adding dilute ammonium hydroxide (NH4OH) until the solution was basic and precipitation occurred.
The mixture was allowed to cool, and the water was removed. The remaining base mixture was allowed to dry overnight. Ten 50 mg portions were combined with 5 ml of hexane in 10 separate 15 ml glassround-bottom centrifuge tubes (five test tubes per solvent). All samples were heated at 75 °C for approximately 5 min. Once the solutions were cooled, 5 ml of water were added to each test tube. The samples were shaken vigorously and centrifuged for 2 min. The solvent layer was removed and washed again with water. The washing process was repeated up to five times (Table 1). The washed solvent was evaporated to dryness and examined via FTIR and GC/FID.
Ion-Pair separations.
Three ion-pair columns were prepared to separate mixtures of cocaine HCl and tetramisole HCl (85:15, 70:30, and 50:50). Fifty mg of cocaine HCl/tetramisole HCl were dissolved in 250 μL of water, combined with 0.5 g of Celite 545, and mixed well. The resulting mixture was transferred to a column packed with a portion of Celite 545 and 1-2 mL of ion pair solution as specified in next Table 2. Cocaine was eluted with 35 mL of water-saturated chloroform. Five 5ml fractions were collected and analyzed via GC/FID for the amount of cocaine present. Appropriate fractions were combined, evaporated to dryness, and examined via FTIR.Resultsand Discussion.
Liquid/liquid Separations.The three mixtures of cocaine base/tetramisole base (85:15, 70:30, 50:50) were dissolved in hexane and washed with water repeatedly. As illustrated in Table 2, tetramisole base in the 85:15 and 70:30 mixtures was completely removed from the hexane after washing with water five times due to its preferential solubility in water versus cocaine. After five washes of the 50:50 mixture, 99+% pure cocaine was obtained.
Ion-Pair Separations.
Three separate columns were prepared with different stationary phase preparations. As shown in Table 3, Column 1 provided the best separation with pure cocaine fractions (PTHIT free) for all three mixtures tested (85, 70 and 50% cocaine HCl).
Pure cocaine fractions were also collected with Columns 2 and 3 for the 85:15 cocaine HCl/tetramisole HCl mixture, however, very small amounts of PTHIT were detected with the 70:30 and 50:50 mixtures. For separation simplementing an ion-pair solution, it is important to determine the salt form of cocaine in the starting material.
Knowledge of the salt form prior to the use of a separation technique (liquid/liquid or ion-pair chromatography) will prevent an analyst from inadvertently altering the salt form of cocaine during the removal of phenyltetrahydroimidazothiazole.
Ion-Pair Separations.
Three separate columns were prepared with different stationary phase preparations. As shown in Table 3, Column 1 provided the best separation with pure cocaine fractions (PTHIT free) for all three mixtures tested (85, 70 and 50% cocaine HCl).
Pure cocaine fractions were also collected with Columns 2 and 3 for the 85:15 cocaine HCl/tetramisole HCl mixture, however, very small amounts of PTHIT were detected with the 70:30 and 50:50 mixtures. For separation simplementing an ion-pair solution, it is important to determine the salt form of cocaine in the starting material.
Knowledge of the salt form prior to the use of a separation technique (liquid/liquid or ion-pair chromatography) will prevent an analyst from inadvertently altering the salt form of cocaine during the removal of phenyltetrahydroimidazothiazole.
Conclusions.
Two techniques were utilized for the separation of cocaine and tetramisole mixtures. GC/FID and FTIR data were obtained to effectively determine the purity and salt form of the recovered cocaine. For mixtures of cocaine base/tetramisole base, the best method to purify the cocaine was a liquid/liquid separation employing hexane and water; five water washes successfully removed tetramisole base from the cocaine. The most successful technique for separation of cocaine HCl/tetramisole HCl utilized an ion-pair chromatographic column packed with 4 g of Celite 545 and 2 mL 1 N HCl/2M NaCl.
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