Opium alkaloids material

The starting material for these 14-hydroxy compounds is the opium alkaloid thebaine (9). Although present in only small amounts in the alkaloid fraction from Papaver somniferum, it constitutes the major component (as much as 26% of the dried latex) from a... 

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]. 

Opium alkaloids such as codeine, thebaine, papaverine, and noscapine exhibit high solubility (0.09-0.9 mg/g) in supercritical fluids including CO N,0, CHF, [37]. However, in spite of their high solubilities, they were not extracted from plant material by pure CO, to the degree expected [29], possibly because these alkaloids exist as their salt forms in plant tissue. In this chapter, the examples that show the difference of the solubilities between alkaloidal free bases and salts are presented. For this comparison, the solubilities of the free bases of hyoscyamine (1), scopolamine (2), pseudoephedrine (6) were measured and compared with those of their hydrochloride salts (Figures 3 and 4). 

Opium has been known and used for 4000 years or more. In recent times, attempts have been made at governmental and international levels to control the cultivation of the opium poppy, but with only limited success. In endeavours to reduce drug problems involving opium-derived materials, especially heroin, where extremely large profits can be made from smuggling relatively small amounts of opium, much pharmaceutical production has been replaced by the processing of the bulkier poppy straw . The entire plant tops are harvested and dried, then extracted for their alkaloid content in the pharmaceutical industry. Poppy straw now accounts for most of the medicinal opium alkaloid production, but there is still... 

The opium alkaloids have engaged the interest of scientists since the isolation of morphine by Sertlirner in 1806. The Isolation, characterization and quantification of these alkaloids have been a continuing challenge. Gas chromatography of opium alkaloids has been performed i.a. for the analysis of the alkaloids present in the crude drug itself, especially for the quantitative determination of morphine, as well as for the analysis of opium alkaloids, mainly morphine - and heroin - in biological materials. Most studies have so far been carried out with packed columns, only a limited number with capillary columns. 

HPLC ANALYSIS OPIUM ALKALOIDS IN PLANT MATERIAL AND OPIUM ... 

The term opium alkaloids has been used rather loosely to cover all narcotic analgesics, whether they be synthetic compounds, partially synthetic, or extracted from plant material. To be precise, we should really only use the term for those natural compounds which have been extracted from opium—the sticky exudate obtained from the poppy (Papaver somniferum). The term alkaloid refers to a natural product which contains a nitrogen atom and is therefore basic in character. There are, in fact, several thousand alkaloids which have been extracted and identified from various plant sources and examples of some of the better known alkaloids are shown in Fig. 12.1. These compounds provide a vast library of biologically active compounds which can be used as lead compounds into many possible fields of medicinal chemistry. However, we are only interested at present in the alkaloids derived from opium. 

Because of their economic interest, biotechnological production of these alkaloids would be of great interest particularly as it could contribute to reduce the illicit production of opium, the raw material for heroin manufacture. As a result, extensive studies have been made on the application of plant cell and tissue culture for the production of opium alkaloids. Furthermore bioconversion of certain semisynthetic products has been studied. A series of patents in this field has been filed (Table XXII). 

EC is currently the most popular method for the determination of morphine in body fluids, since morphine contains a phenol group which is easily oxidized (Tagliaro et al. 1989). The detection limit of morphine typically varies from a few tens of picograms to several hundred. Other opiates contain a tertiary alicyclic amine, and can best be detected using a neutral or slightly alkaline eluent and about a 0.3-0.4 V higher potential than for morphine (Schwartz and David 1985). For the nonphenolic alkaloids, codeine has been detected by EC in body fluids at the nanogram level. However, EC has seldom been used for the determination of opium alkaloids in plant material. 

Consequent upon the need for genetic assaying of opium alkaloids for germplasm enhancement and for their efficient exploitation in pharmaceuticals, chemical analysis of these alkaloids is imperative, and entails chiefly the isolation and quantification of different alkaloids. The quantitation is further marked by separation (from each other) and measurement of each alkaloid. Further, methods of chemical analysis may be delineated into those specific for plant materials (crops), or classes of chemical compounds (alkaloids, steroids, glycosides, etc.). They may also be categorized in relation to technological and instrumental inputs. However, in this chapter, we present models which are, by and large, not specific to plant material, class of substance, or instrumentation tools. 

In modem medicine, mily the purified opium alkaloids and their derivatives are commonly employed. Although the ripe poppy capsule can contain up to 0.5 % total alkaloids, opium represents a much concentrated form and up to 25 % of its mass is composed of alkaloids. Of the many (>40) alkaloids identified, some six represent almost all of the total alkaloid content. Actual amounts vary widely, e.g., morphine (4-21 %), codeine (0.8-2.5 %), thebaine (0.5-2.0 %), papaverine (0.5-2.5 %), noscapine (narcotine) (4—8 %), and narceine (0.1-2 %). A t3q>ical commercial sample of opium would probably have a morphine content of about 12 %. Powdered opium is standardized to contain 10 % of anhydrous morphine, usually by dilution with an approved diluent, e.g., lactose or cocoa husk powder. The alkaloids are largely combined in salt form with meconic acid, opium containing some 3-5 % of this material. Meconic acid is invariably found in opium but, apart from its presence in other Papaver species, has not been detected elsewhere. It gives a deep red-colored complex with ferric chloride, and this has thus been used as a rapid and reasonably specific test for opium. Of the main opium alkaloids, only morphine and narceine display acidic properties, as well as the basic properties due to the tertiary amine. Narceine has a carboxylic acid function, while morphine is acidic due to its phenolic hydroxyl. This acidity can be exploited for the preferential extraction of these alkaloids (principally morphine) from an organic solvent by partitioning with aqueous base (Table 15.6). 

The actions of the naturally occurring materials now known as alkaloids were probably utilized by the early Egyptians and/or Sumarians (1). However, the beginnings of recorded, reproducible isolation from plants of substances with certain composition first took place in the early nineteenth century. Then in close succession, narcotine [128-62-1] (1, now called noscopine, C22H23NOy) (2) and morphine (2, R = H) (3) (both from the opium poppy, Papaver somnijerum E.) were obtained. 

The Opiates. The International Narcotics Control Board—Vienna, tracks the tick production of narcotic dmgs and annually estimates world requkements for the United Nations. Thek most recent pubHcation (100) points out that more than 95% of the opium for Hcit medical and scientific purposes is produced by India and, in a declining trend, only about 600 t was utilized in 1988. This trend appears to be due to the fact that the United States, the largest user of opium for alkaloid extraction, reduced the amount of opium being imported from about 440 t in 1986 to 249 t in 1987 and 224 t in 1988. The United States used about 48 t of morphine (2, R = H) in 1988, most (about 90%) being converted to codeine (2, R = CH3) and the remainder being used for oral adrninistration to the terminally ill (about 2 t) and for conversion to other materials of minor commercial import which, while clearly alkaloid-derived, are not naturally occurring. 

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. 

Archaeological evidence shows that early civilizations were keenly aware of the medicinal properties of certain plants. In a.d. 78, for example, the Greek physician Dioscorides wrote Materia Medica, a treatise in which he described about 600 plants known to have medicinal properties. Included in this list was the opium poppy, shown in this chapter s opening photograph. Incisions in the seed capsules of this plant yield a milky sap. When air-dried and kneaded, the sap forms a soft material known as opium, which contains opioids, a class of alkaloids known for their pain-killing and tranquilizing effects. The molecule shown is morphine, one of the more abundant and potent opioids. 

In order to extract the morphine, the opium resin must first be prepared. This is achieved by adding the raw opium to boiling water, in which the alkaloids dissolve, while the insoluble material can be removed while it floats, or is filtered from the solution. To extract the morphine from the processed opium, the latter is placed in a large volume of boiling water and calcium hydroxide added. The water is cooled and the unwanted alkaloids precipitate, while the morphine and some codeine remain in solution. The solution is then re-heated and ammonium chloride (and sometimes ethanol and diethyl ether) added. When the pH reaches 8-9, the... 

A number of various derivatization reactions have been used, as shown in Table 14.25. The derivatization has been carried out as off-column or on-column derivatization, mostly in order to give morphine and related alkaloids with phenolic or alcoholic hydroxyl groups better gas chromatographic properties. Especially for quantitative determination of morphine in opium or biological material such derivatization was necessary. Street et al. found, however, that the problem of adsorption of a phenolic alkaloid, such as morphine, because of "active sites" on the solid support could be solved by deactivation of the solid support by treatment of it (diatomaceous earth) with benzoyl chloride in pyridine before coating it with the stationary phase. 

Coca leaves (Erythroxylum coca) have been used in South America since the time of the Incas, if not longer. Although the habit of coca chewing is usually attributed to the extremes of altitude and climate, other causes, such as malnutrition and adverse social, educational, and economic factors, are probably of more importance (278). As with opium, use of the crude plant material does not produce so dramatic a syndrome as does the use of the pure alkaloid (279). Nevertheless, in spite of the often-repeated statement that the use of coca increases resistance to fatigue and is harmless and possibly beneficial in its natural environment, the fact remains that it undermines the physical and mental health of the population and thus leads to a deterioration of the very living conditions that caused it (280). 

Opium was known to man many centuries ago. This is evident from the Ebers Papyrus and Homer s Odyessey where the use of opium was mentioned. Opium is obtained by making superficial incisions on the immature and unripe capsules oiPapaver somniferum (or poppy plant). The exudate is air-dried and then powdered to give the official powdered opium. A systematie study of the plant material led to the isolation and identification of the most important alkaloid known as morphine in 1803. Other alkaloids isolated from opium include codeine, papaverine and thebaine. 

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