STUDIES ON THE ANALYSIS OF SOME ALKALOIDS OF PHARMACEUTICAL AND TOXICOLOGICAL IMPORTANCE

Abstract

Alkaloids are the nature's precious gifts to mankind and find an ever increasing utility in comforting various human ailments. The first use of the word 'alkaloid' is attributed to Mlessner, originally meaning 'like an alkali', it eventually became defined as a 'nitrogenous vegetable base". This definition has served quite well for over a hundred years but now in the light of modern context it seems rational to widen the scope of the term 'alkaloid' to include some more compounds of basic nitrogen of pharmacological or physiological interest and to qualify the word with such epithets as 'plant' or 'synthetic' whenever such qualification is necessary. Despite many laboratory created synthetics of pharmacological importance, there is always a growing scientific interest in returning to nature's healing handouts. The medicinal applications of alkaloids range from analgesic to cardiac stimulants. Numerous examples are known In literature depicting their versatile utility in drug therapy. Some alkaloids might even rate a place beside history's great cures. Pain-killing morphine from the double-edged gift of opium poppies, quinine — the tamer of malaria from the bark of cinchona, reserplne — a forerunner of the modern tranquilizers from the root of Indian Rauwolfia serpentina, oil from the seeds of the chaulmoogra tree — a drug considered for long as the only one effective for arresting the frightful progress of leprosy, and cocaine — a valuable tool in local anaesthesia from coca leaves can be cited as some of the many examples to throw light on the wide use and importance of alkaloids as miraculous medicines in the present day society. Incidentally, most of the alkaloids are extremely toxic if consumed above the prescribed dose. And, hence, they find an use as homicidal and suicidal agents. Poisoning by alkaloids in man is common, whether intentionally or by their injudicious use, and still continues to be very much prevalent in India. A survey by Tewari1 revealed that 33 percent of the poisoning cases in India were due to alkalokls or substances containing them, the total including significant number of cases of opium, datura and strychnos alkaloids. Thus, the alkaloidal poisoning still remains a serious problem2 mainly due to the easy availability of the plants bearing these toxic alkaloids. Also,the poisoning by alkaloids in animals is quite frequent and may be due to the ingestion of the plant or doping of the race animals. Thus,the miraculous medicinal properties and the potent poisonous nature of the alkaloids has lead to their widespread use and abuse creating many medicosocio- legal problems which make people from wide ranging professionSjlike pharmacologists, toxicologists and forensic scientists,interested in their trace analysis. As such,the interest in the analysis of alkaloids is interdisciplinary in nature. The problem of analysis of alkaloids has been drawing the attention of chemists right from the days of Orfila (1821) 3 and since then significant contributions have been made in this field, Inspite of all the work done, the analysis of alkaloids still continues to be one of the topical problems of organic analytical chemistry. The need is always being felt to develop sensitive and selective methods of their determination and rapid and convenient procedures for separation. For the present study,two important groups of alkaloids namely opium and strychnos have been selected mainly because of the mind-enslaving narcotic action of the former and the extreme toxicity of the latter. The alkaloids chosenare morphine, codeine, thebaine, narcotine, papaverine, strychnine and brucine. A brief description of their medicinal and toxic properties may justify their selection. Crude opium finds medical use as an analgesic and antidiarrheatic; in larger doses death from respiratory paralysis may be produced. Morphine finds therapeutic use as an unparallelled vanquisher of pain, as a central nervous system depressant, antiemetic and as diaphoretic agent. Codeine, papaverine and narcotine have antitussive and antispasmodic action on smooth muscle and are used to relieve bronchial or intestinal spasms and in obstetrics. Papaverine causes light narcosis; in over doses,tetanus and respiratory paralysis may result. Codeine in large doses produces exhilaration, hypotension, miosis and tachycardia. Thebaine is a violent tetanic poison. Incidentally, the opium containing the above mentioned alkaloids constitutes the largest and probably the most important 4 class of drugs of addiction because of the narcotic action. It has become the subject and object of illicit drug-trafficking all over the world. As such,its control is an international problem. Strychnine has been used in therapeutic doses, to stimulate respiratory and vasomotor nerve centres. In higher doses, it acts on spinal cord leading to convulsions and tetanus; death usually follows from respiratory exhaustion. Besides, it Is used as a rodenticide and vermin killer. Brucine has practically no therapeutic value but is chiefly used as a denaturant of alcohol and oils. The ready availability of opium and strychnos alkaloids or their sources,and their toxicity lead to their becoming one of the most common causes of suicides and homicides. Mostly, these alkaloids are present in trace amounts in toxlcological specimens and,as such,there is a growing demand for the development of sensitive methods of analysis. All this,together with the immense importance of these alkaloids,kindled the interest of the author to carry out some investigations on their analysis. Because of the varied interest in the subject,a variety of methods have been employed for the analysis of alkaloids. There 3-14 are already a number of books and reviews dealing with alkaloid analysis. Further, much useful information regarding the various analytical aspects of alkaloids can be had from •Fundamental Reviews' and 'ApplicationReviews' published yearly in 'Analytical Chemistry' journal. Several papers on the analysis of alkaloids are being published in applied journals dealing with analytical biochemistry, toxicology and pharmacology etc. A fairly good number of them appear in journals which are less readily available or in languages other than English. As such, the literature Is very much scattered,thus,making it a difficult task to keep track of the ever Increasing information. However, an attempt has been made by the author in the thesis to cover and discuss the literature in a reasonably justifiable manner from the information gathered from some easily available journals, chemical abstracts, analytical abstracts and chemical titles. A skeletal representation of the different aspects of the analytical chemistry of alkaloids can be made as follows: A DETECTION B SEPARATION C QUANTITATION Physical methods (UV, visible, IR spectrophotometry. X-ray and melting point studies) Chemical methods (colour reactions, precipitation and crystal tests) Biological methods Extraction Chromatography (paper, thin layer, gas liquid (GLC), high pressure (HPLC) and ion exchange) /Volumetric (aqueous, nonaqueous, heterometric and complexometric) Gravlmetry Instrumental (spectrophotometry, epectrofluorlmetry, polarography. amperometry, radtametry and radloimmuno assay for morphine and related surrogates) The Initial task of the analysis of an alkaloid either in pure state or after its isolation is its detection, generally at very low concen* trations. Out of the different methods available for the detection of alkaloids,the colour reactions offer a great promise mainly because of their sensitivity and simplicity. Unlike the physical methods of detection these do not at all involve any costly equipment. Moreover, the colour reactions are rapid and can be applied from tracer levels to macro concentrations. fa the analysis of these alkaloids when present in a mixture, many a times,their separation becomes a necessity. Moreover, in toxicologlcal and forensic analysis the alkaloids have to be separated In order to establish their identity. Chromatography has often been the choicest method for the purpose. Out of the many chromatographic techniques, paper and thin layer chromato graphy are widely used due to their simplicity, rapidity, convenience and Inexpensive nature, fa thin layer chromatography,most of the adsorbents used will stand high temperatures and corrosive acids. The choice of different adsorbents and solvents will result into high efficiency of the technique in resoluting the mixtures, thus making It indi spensable for toxicologist, hospital biochemist, and forensic chemist. Though HPLC gives rise to fresh hopes for research and possesses inherent advantages over some chromatographic methods. It Is of comparatively little value for routine screening because of the prohibitive cost Involved. GLC, in the words of Eric Heftman, is not a much preferred technique in alkaloidal separation 7 because of their nonvolatile nature. Hence,GLC seems to be of secondary Importance In the field of alkaloidal analysis. Moreover, both these techniques require reasonably pure samples free from any extraneous matter and,hence,need a pre-sample clean-up.