Opium separation

The synthesis of dextromethorphan is an outgrowth of early efforts to synthesize the morphine skeleton. /V-Methy1morphinan(40) was synthesized in 1946 (58,59). The 3-hydroxyl and the 3-methoxy analogues were prepared by the same method. Whereas the natural alkaloids of opium are optically active, ie, only one optical isomer can be isolated, synthetic routes to the morphine skeleton provide racemic mixtures, ie, both optical isomers, which can be separated, tested, and compared pharmacologically. In the case of 3-methoxy-/V-methylmorphinan, the levorotatory isomer levorphanol [77-07-6] (levorphan) was found to possess both analgesic and antitussive activity whereas the dextrorotatory isomer, dextromethorphan (39), possessed only antitussive activity. Dextromethorphan, unlike most narcotics, does not depress ciUary activity, secretion of respiratory tract fluid, or respiration. 

Estimation of Other Alkaloids in Opium. Of the other alkaloids the most important is codeine, and processes for its estimation in opium have been described by Cespari, Andrews,and Annett and co-workers methods for its assay in admixture with other drugs in tablets and other products are also available. The estimation of papaverine has been described by Issekutz,i and of narcotine by Snesarov. As to methods for the separation and estimation of two or more of these subsidiary alkaloids, codeine and narcotine have been dealt with by van der Widen,narcotine and papaverine by Annett and Bose, ( and the bromination of codeine and narceine has been studied by Vaisberg et al. with a view to estimation by this means. 

The first scheme for the separation of the six chief alkaloids of opium, VIZ., morphine, codeine, thebaine, papaverine, narcotine and narceine, is probably that of Plugge. Much later Kljatschkina investigated for each of these six bases the properties by means of which isolation and estimation could probably be effected and, on the basis of the results, devised a plan for such analyses. More recently Anneler has published a detailed account of a scheme with the same objective. l Attention had already been given to complex, systematic analyses of this kind, in connection with examination of the mixtures of opium alkaloids, which have long been in use in medicine in these at first only morphine and other alkaloids were determined, but in the more recent schemes provision is made for the estimation of each alkaloid. ... 

The processes used in the manufacture of morphine are believed to be still based on that described by the Scottish chemist Gregory,in 1833, with improvements devised by Anderson. A description has been published by Schwyzer, who also deals with the manufactme of codeine, narcotine, cotarnine, and the commercially important morphine derivatives, diamorphine (diacetylmorphine), and ethylmorphine (morphine ethyl ether). More recently Barbier has given an account of processes, based on long experience in the preparation of alkaloids from opium. Kanewskaja has described a process for morphine, narcotine, codeine, thebaine and papaverine, and the same bases are dealt with by Chemnitius, with the addition of narceine, by Busse and Busse, and by Dott. It is of interest to note that a number of processes for the extraction and separation of opium alkaloids have been protected by patent in Soviet Russia. ... 

Papaverine, C20H21O4N. This alkaloid, first obtained by Merck, occurs in the mixture precipitated by ammonia from the mother liquors of opium extract from which morphine and codeine have been separated in Gregory s process, and methods for its isolation from this mixture have been published by Hesse and others. The alkaloid may be purified by conversion into the acid oxalate, B. H2C2O4, m.p. 196° or 201-5-202°, which is nearly insoluble in alcohol. 

Thebaine, CjgHgiOgN. This base, which occurs in opium to the extent of 0-1 to 1 per cent., was first obtained by Pelletier and Thiboumery, who regarded it as isomeric with morphine, and named it paramorphine. It was examined by Kane, who first called it thebaine, and by Anderson, who described a method of isolation and provided the formula given above. It remains in the mother liquor after the removal of morphine and eodeine hydrochlorides in Gregory s process, and in Hesse s method of isolating it from this source is obtained as the acid tartrate. This is crystallised from hot water, and the alkaloid regenerated from it is reerystallised from dilute alcohol, from which it separates in leaflets, or from dry alcohol in prisms, m.p. 193°, — 218-6° (EtOH) or — 229-5°... 

Opium contains over 40 different alkaloids, all of which will be exuacted from opium by the procedure just described. It then remains to separate morphine from this mixture. Of the main opium alkaloids, only morphine displays some acidic properties as well as basic properties. Although a tertiary amine, morphine also contains a... 

Capillary electrophoresis is suitable for use to separate a wide spectrum of both large and small biological molecules. This method was used for analysis of opium alkaloids such as thebanine, codeine, morphine, papaverine and narcotine. 

Dams et al. [19] determined seven different opium alkaloids and derivatives in seized heroin using fast LC-MS analysis. Analytes were separated in 5 min on a monolithic silica column with a gradient elution system and an optimized flow of 5 mL/min. Detection was carried out using a sonic spray ion source [20] a modified ESI source were ionization is achieved using a nebulizer gas at sonic speed instead of applying an electrical field. 

The assumption which is made in the type of test deseribed following is that the related unknown substances will produce a similar intensity of spot to the test substance itself at equal concentrations. For example, a limit test is conducted for related (foreign) alkaloids in codeine, which is extracted from the opium poppy in which a range of alkaloids occur thus, the exaet identity of the impurities may not be known. To conduct the test, 10 pi amounts of three solutions are applied separately to a TLC plate. The solutions contain 4.0% w/v codeine (Solution 1),... 

Coenegracht et al. [3] have introduced a four solvent system to compose mobile phases for the separation of the parent alkaloids in different medicinal dry plant materials, like Cinchona bark and Opium. Through the use of mixture designs and response surface modeling an optimal mobile phase was found for each type of plant material. These new mobile phases resulted in equally good or better separations than obtained by the procedures of the Pharmacopeias. Although separations were as predicted, the accuracy of the quantitative predictions needed to be improved. 

Therefore the influence of temperature and humidity on the robustness will be investigated. The maximum number of alkaloids to be separated in the paper of Coenegracht et al [3] was six in opium, and the separation of seven alkaloids in this paper is a severe test of the four solvent systems suitability for the separation of alkaloids. The alkaloids are strychnine, quinine, narceine, heroin, noscapine, caffeine and papaverine. 

Heptoses and higher sugars may similarly be separated, and the identity of D-erythro-c-galacto-nonulose in avocado was determined by comparison of its gas-chromatographic behavior with that of a synthetic sample.336 Higher sugars have been separated, and identified, from avocado,151 Pichi,337 opium poppy,338 and bacterial lipopoly-saccharides.339... 

ILs have been used in the CE-electrochemiluminescence (ECL) method to determine bioactive constituents in Chinese traditional medicine [58]. CE/Tris(2,2-bipyridyl) ruthenium(II) (Ru(bpy)3 +) ECL, CE-ECL, with an IL detection system was established to determine bioactive constituents in Chinese traditional medicine opium poppy, which contains large amounts of coexistent substances. Running buffer containing 25 mM borax-8 mM [C2CiIm][BF4] (pH 9.18) was used, which resulted in significant changes in separation selectivity and obvious enhancement in ECL intensities for those alkaloids with similar structures. Quantitative analysis of four alkaloids was... 

The two liquid layers of ATPS are aqueous solutions. Since their introduction by Albertson, ATPS have proved extremely useful to separate and purify biological material, especially proteins [8]. Earlier fhey were used in CCC for fhis purpose [9-10]. If has been reported recently that [C4Cilm]Cl, a fully wafer-soluble IL, is able to form fwo aqueous phases when K2HPO4 is added to ifs solution [11]. This biphasic system was used to fractionate opium alkaloids, demonstrating its ability to dissolve molecules of intermediate polarity differently [12]. 

Liquid chromatography is two decades more mature than capillary electrophoresis. As trained electropherographers become more common, more separations will be handled by electrophoresis. For example, electrophoresis displaced liquid chromatography as the preferred method for forensic analysis of alkaloids in opium and heroin.51 The enabling technology for this application was dynamic coating of the capillary between runs to eliminate adsorption of analytes on the silica surface and decrease variations in migration times to less than 0.5%. 

Morphine is the most active part of opium, a pure chemical isolated from the dried sap of the unripe poppy pod. Even today, morphine is still made from poppies. It is the prototype opiate, the parent from which all the others sprang. But efforts over the past two centuries to separate the beneficial aspects of opiates from their social drawbacks have failed. Even totally synthetic drugs that mimic morphine and the other opiates remain utterly linked to addiction. 

N. R. Ayyangar, S. Biswas, and A. Tambe, Separation of opium alkaloids by TLC combined with flame ionization detection using the peak pyrolysis method, J. Chromatogr., 547 538 (1991). 

Janicot et al. presented the separation of opium alkaloids using sub-critical and supercritical fluid chromatography [20]. Carbon dioxide-meth-anol-triethylamine-water mixtures were used as the mobile phase with packed aminopropyl or bare silica columns. The influence of aminated polar modifiers such as methylamine, ethylamine, and triethylamine was studied. Figure 7.15 shows the separation of six opium alkaloids narcotine, papaverine, thebaine, codeine, cryptopine, and morphine on a Lichrosorb Si-60 column. The method gave comparable results with HPLC. 

Figure 7.15 Separations of opium alkaloids on bare silica. Column = x 0.46 cm ID stationary phase, 5-/im LiChrosorb Si-60 silica mobile phase, carbon dioxide-methanol-methylamine-water (83.37 16.2 0.15 0.23, w/w) Solutes 1, narcotine 2, papaverine 3, thebaine 4, codeine 5, crytopine 6, morphine. [Reprinted from Ref.20, J. Chromatogr. 437, 351 (1988) with kind permission of Elsevier Science Publishers, The Nether-, lands.]...

J.L. Janicot, M. Caude, and R. Rosset, Separation of opium alkaloids by carbon dioxide sub- and supercritical fluid chromatography with packed columns Application to the quantitative analysis of poppy straw extracts, J. Chromatogr., 437 351 (1988). 

A. Gyeresi and G. Racz, New solvent for separation of the main alkaloids of opium (by thin-layer chromatography), Pharmazie, 28 211 (1973). 

Crystals which darken at about 240 and decompose at about 283 . Practically insoluble in water hence ease of separation from other opium alkaloids. 

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