Amphetamines, extraction

Fales and Pisano (30) were the first to describe the gas chromatographic analysis of amphetamine. They used 4% SE-30 in a silanized glass column and an argon ionization detector for the separation of (3-phenethylamine, amphetamine, norephedrine, eph drine, histamine, tyramine, dimethyltriptamine, tryptamine, 5-methoxytryptamine, benzylamine, N-methylbenzylamine, octopamine, synephrine, normetanephrine, serotonin, N-acetyltryptamine, find melatonin. The method was also used for the analysis of amphetamine extracted from urine. 

Of course, there are a couple advantages to using HCI as the hy-drolyzer. Since using hydrochloric acid means that all that fat MDA or amphetamine is in the water solution, the chemist can vacuum filter the solution to get rid of all the tar and crap which will give a remarkably clean water solution. The X is released by basifying and extracting with solvent. 

A much greater yield can be had if the chemist uses carbitol as a solvent instead of propanol [62]. Carbitol is a really hazardous solvent and should not be breathed or placed on one s skin. The reaction proceeds exactly as before except that after 24 hours of reflux and cooling the mixture is slowly poured into 1500mL ice cold dH20. The upper solvent layer is separated and the aqueous layer extracted with 200mL ether which is then combined with that upper solvent layer. The combined solvent portions are vacuum distilled to afford safrole-azide (or phenylisopropyi-azide for amphetamine) with the yield rising to 70%. 

In a recent report, HS-SPME was used for the extraction of amphetamines from human hair (142). Human hair analysis is gaining interest in the analysis of drugs of abuse, since it offers attractive features easy and unlimited sampling, and as the... 

Connor J. D, Ruston A, Eyasu M. Comparison of effects of khat extract and amphetamine on motor behaviors in mice. J Ethnopharmacol 2002 81 65-71. 

Cathinone An amphetamine derivative found in khat extracted from Catha edulis growing in the Horn of Africa, where it is widely used as a recreational stimulant. 

Drugs have been purified by SPE in the analysis of amphetamine (AM) by Kaleta et al. [98], by various consecutive washing steps with hexane in the analysis of methamphetamine (MA) by Jones-Lepp and Stevens [99], and by simple centrifugation after addition of water, to separate the aqueous extract from a bottom sediment layer and a top fat layer, in the analysis of AM, MA, cocaine (CO), and benzoylecgonine (BE) by Langford et al. [100], who found little improvement in reducing matrix effects when applying SPE cleanup. 

FIGURE 1.32 Extraction-time profiles for promethazine (A), methadone (B), amphetamine (C), pethidine (D), and haloperidol (E) in 1 mL sample volume with 0, 5, and 50% methanol added to plasma sample.155 (Reproduced with permission from the Royal Society of Chemistry.)... 

Musshoff, F., Lachenmeier, D.W., Kroener, L. and Madea, B. (2002) Automated headspace solid-phase dynamic extraction for the determination of amphetamines and synthetic designer drugs in hair samples. J. Chromatogr. A 958, 231-238. 

To a cooled and stirred solution of 100 ml acetonitrile and 64.8 g mercuric nitrate, add slowly 0.2M of the allylbenzene (keep temperature below 30°). Stir one hour at room temperature, cool and add 200 ml 3N NaOH, then 200 ml 0.5M NaBH4 in 3N NaOH. After one hour saturate the water layer with NaCI and extract with ether. Dry and evaporate in vacuum the extract to get the N-acetyl-amphetamines. This procedure may not work with the propeny I benzenes. 

Add 0.44 moles ring substituted phenylacetate, 100 g acetic anhydride and 30 g sodium acetate and heat at 145-150° for 18 hours to get ca. 0.4 moles of the methyl-phenylacetate (I). Add (I) and formamide (or N-methyl-formamide for the N-methyl cpd.), heat 4-5 hours at 180-195°, cool and extract with CHC13. Evaporate in vacuum, dissolve residue in 40% sulfuric acid and heat at 90-125° for 5-6 hours. Neutralize and add solid NaOH to precipitate about 50% amphetamine. Treat with 10% sulfuric acid to get the sulfate. 

M p-methoxy (or other group)-Br-benzene (see this paper for prepartion) and 4.6 g Mg. Rapidly add 18.5 g chloroacetone in 50 ml ether. Evaporate the ether by heating in oil bath and then at about 135° for one hour. Cool and add ice and dilute HCI extract the oil with ether and dry, evaporate in vacuum to get about 11 g product (can distill 106/18). 0,057 M of the ketone product in 16 g formamide in 100 ml round bottom flask, with an air condenser. Heat twelve hours at boiling and then reflux with 35 ml 30% NaOH eleven hours and separate the amine layer and dry, evaporate in vacuum to get the amphetamine. 

Several other methods have been published using RP-HPLC for the determination amphetamines and related derivatives. Studies have shown the determination of amphetamine and related derivatives in plasma, urine, and hair by RP-HPLC with precolumn derivatization and either UV/VlS or fluorescence detection. Various methods are employed by SPE technologies using Cl8 cartridges for sample cleanup prior to derivatization. The derivatized compounds were separated on analytical columns of various Cl 8 bonded phase materials. The methods generally used water/acetonitrile mobile phases operated in gradient mode. All studies reported extraction recoveries of 85-102% for all the analytes, with LLOQs ranging from 5 to 60 ng/ml (Tedeschi et al., 1993 Ealco et al., 1996 Hernandez et al., 1997 Al-Dirbashi et al., 1997 Al-Dirbashi et al., 2000 Soares et al., 2001). 

Hernandez R, Falco P, Cabeza A. 1997. Liquid chromatographic analysis of amphetamine and related compounds in urine using solid-phase extraction and 3,5-dinitrobenzoyl chloride for derivatization. J Chromatogr Sci 35(4) 169-175. 

Yonamine M, TawU N, Moreau RL, Silva OA. 2003. Solid-phase micro-extraction-gas chromatography-mass spectrometry and headspace-gas chromatography of tetrahydrocannabinol, amphetamine, methamphetamine, cocaine and ethanol in saliva samples. J Chromatogr B Anal Technol Biomed Life Sci 789 73. 

When using PFT with a neutral selector, it is quite difficult to avoid any entrance of the chiral selector into the ionization source, particularly at a high pH, where EOF is important. The use of BGE at low pH and/or coated capillary to minimize EOF is therefore mandatory. However, the coaxial sheath gas, which generally assists the ionization process, leads to an aspirating phenomenon of the chiral selector in the MS direction. Javerfalk et al. were the first to apply PFT with a neutral methyl-/i-CD for the separation of racemic bupivacaine and ropivacaine with a polyacrylamide-coated capillary and an acidic pH buffer (pH 3). Cherkaoui et al. employed another neutral CD (HP-/1-CD) with a PVA-coated capillary for the analysis of amphetamines and their derivatives. To prevent a detrimental aspiration effect, analyses were carried out without nebulization pressure. Numerous other studies presented excellent results such as the enantioselective separation of adrenoreceptor antagonist drugs using tandem mass spectrometry (MS/MS) the separation of clenbuterol enantiomers after solid-phase extraction (SPE) of plasma samples or the use of CD dual system for the simultaneous chiral determination of amphetamine, methamphetamine, dimethamphetamine, and p-hydroxymethamphetamine in urine. 

FIGURE 4 Chiral CE ESI/MS analysis of five amphetamine derivatives and two pharmaceutical compounds. Total ion current (TIC) and extracted ion currents (XIC) of amphetamine (A), methamphetamine (MA), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), and methylenedioxyethylamphetamine (MDEA), and tramadol (TMD) and methadone (MTD) in plasma after LLE with electrokinetic injection. 

Boatto, G., Nieddu, M., Carta, A., Pau, A., Palomba, M., Asproni, B., and Cerri, R. (2005). Determination of amphetamine-derived designer drugs in human urine by SPE extraction and capillary electrophoresis with mass spectrometry detection.. Chromatogr. B 814, 93—98. 

Another Hydrogenation with Platinum Oxide. JACS, 55, 2694. This method is used to reduce those hydrox-mandelonitriles in the amphetamine section. It uses low pressure and can be used on about any reducible compound. It can also use palladium oxide as the catalyst. A solution of 35.8 g of phenyl-2-propanol in 250 ml of 80% ethanol containing 7.3 g of HCl is hydrogenated for 3 hours in a Parr hydrogenation bottle at 3,5kg/cm or 50 p.s.i, over 0,5 g of platinum oxide (or palladium oxide Raney nickel may also work) or an equimolar ratio of analog catalyst for about 3 hours. Filter off the catalyst and rinse with a little water to wash all the product from the catalyst. Dilute the filtrate to 1 liter of volume with water and extract twice with ether to remove any acid insoluble material. The ether extracts do not contain product. The aqueous layer is made alkaline with solid NaHCOs to a pH of 8-9 and the basic oil which separates is extracted with two 300 ml portions of ether. This ether solution is dried over MgS04, and filtered, then evaporated to remove the ether. To convert to the oxalate, add ether to the crude product and add to a solution of 9.6 g of oxalic acid dihydrate in a small volume of methanol. Give ample... 

Forensic analysis of street drugs include that of cocaine together with excipients frequently encountered (579), amphetamines 080), and dyes found in heroin samples 081). An on-line photochemical derivitization of cannabinoids has been described 082). Other pharmaceutical agents studied in formation include nortriptyline in tablets. 083), glycyrrhizic acid from licorice extract 084, 585), pirimiphos methyl 086), digitalis glycosides 0S7), pilocarpine 088), and its antagonist atropine 009). 

Amphetamine was once used in nasal inhalers but was banned in 1959 because abusers removed the inner filling and chewed it. Now propylhexedrine, with about half the potency of amphetamine, is used. This still causes problems in that some desperate souls will leach the compound from the inhaler s cotton wick and inject the extract (called "crank"). This presents all kinds of... 

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