CHEMICAL INTRODUCTION. Summary of symptoms exhibited by various poisons: (1) Sudden death—(2) Insensibility—(3) Vomiting—(4) Action on the eye—(5) Convulsions—(6) Chronic poisoning. Alkaloids, chemically and physiologically—Processes for their detection—Necessity for keeping the extracts separate—Dragendorff’s process—Dr. Guy’s sublimation process—Effects on animals—Doubtful value of this test—Preparation and effects of reagents: (1) Mayer’s—(2) Potassium tri-iodide—(3) Sonnenschein’s test—(4) Bismuth—(5) Phosphotungstic acid—(6) Picric acid—(7) Animal charcoal—(8) Platinic chloride—(9) Tannin or tannic acid—(10) Phospho-antimonic acid—(11) Silico-tungstic acid—(11) Auric, palladium and mercuric chlorides—Ptomaines or cadaveric alkaloids; difficulties raised by their discovery—Principles to be observed in analysing. Before proceeding to a separate examination of the poisons used in the following trials, it will be advisable to take a general view of poisons, specially noticing those that we have selected as the most important legally. They do not admit, perhaps, of accurate classification, but inasmuch as the manner of death and symptoms are usually the most available indication as to the nature of the poison that has acted, the following arrangement will be serviceable. The heads indicate the most prominent symptom: I. Sudden Death.—Large quantities of any poison might be rapid in fatal result, but the sudden poisons proper are:—concentrated sulphuric, nitric, and hydrochloric acids; poisonous gases and vapours, such as carbonic acid and sulphuretted hydrogen (see Casper’s Forensic Medicine, Case CCXLI.), carbonic oxide, arseniuretted and antimoniuretted II. Insensibility, generally following nervous excitement. Morphia and opium; henbane (Hyoscyamus); stramonium; belladonna; nicotine (tobacco); darnel (lolium temulentum); hemlock (Conium maculatum); water hemlock (Œnanthe crocata); fool’s parsley (Æthusa cynapium), [Dr. J. Harley shows that this is not so poisonous as believed: see St. Thomas’s Hospital Reports, x. 25]; Indian hemp (Cannabis indica); Woody Nightshade (Solanum dulcamara); Solanum nigrum; the berries of Potato (Solanum tuberosum); Lobelia inflata: Foxglove (Digitalis); cocculus indicus; certain fungi (notably Amanita muscaria); chloroform; chloral; butylchloral —“croton chloral”): amylene; methylene dichloride; sulphuretted hydrogen; carbonic oxide; and many other substances usually classed as narcotics. III. Vomiting.—Irritant poisons, such as acids, alkalies, alkaline salts in considerable doses (even common salt has proved fatal: see Christison IV. Action on the Eye.—Opium and morphia, calabar bean, aconite (?), and strychnia, contract the pupil: belladonna, henbane, tobacco, stramonium, digitalis and hemlock, dilate the pupil. The effect is often temporary, and sometimes V. Convulsions.—Strychnia, brucia, and some fungi: but this symptom is by no means confined to these, and may even result as tetanus, from disease or irritants (see Trial of Palmer). Morphia, in rare cases, has also caused it. VI. Chronic Poisoning, prostration and wasting. Antimony, mercury, and lead in small repeated doses. With the two latter, but more especially with lead, there is a blue line at the edge of the gums; constipation and colic, paralysis and trembling of the limbs. As lead frequently occurs as an impurity in food, and also may be absorbed by those working with it, these symptoms may be often accidental. Mercury also is given, less than of old, it is true, but still systematically by some, as a regular course in syphilis, &c.: also to children in teething powders. Antimony has been almost abandoned in medicine, from its depressant effect. In these cases, motive, amount, and necessity of dose, and right to administer, must be considered before wilful poisoning can be proved. The analysis, therefore, must be strictly quantitative, which is fortunately tolerably easy. The above summary is by no means perfect, since there are minor differences in each class, which may sometimes rise into such prominence as to confuse the classification. But in medical evidence on the individual poisons of which we treat, those physiologically resembling them in action are always most heard of at the trial, and questions are asked whether this or that may not produce the same symptoms; and hence it is well to direct attention to the analogues of our types. The primary idea of an alkaloid is derived from its resemblance to an alkali. Alkaloids are often called also “Organic Bases.” Their names terminate in—ia or ine. Chemically, the alkaloids are derived from ammonia (NH3) by substituting various organic groups or “compound radicles” (compounds of carbon and hydrogen), for the hydrogen of the ammonia. They are therefore “compound ammonias,” or “amines.” Nitrogen, carbon, and hydrogen, are always present in natural alkaloids, the non-volatile ones, including the greater number, also contain oxygen. Physiologically, alkaloids as a class have a powerful action on the human and animal frame. The medicinal properties of plants are generally due to these substances, though many are still undiscovered or imperfectly known. They exist in the plant combined with vegetal acids, some of which are characteristic, as aconitic acid in aconite, meconic in opium, igasuric (?) in nux vomica, &c. The very small quantity which may sometimes be fatal (a fraction of a grain of the pure alkaloid), the indefiniteness of many of their chemical reactions, and the facility with which they decompose if too high For extracting the alkaloids from animal matters the following process has been used by the author. Mince finely, digest with rectified spirit and enough acetic acid to just acidify, warm to blood-heat for 15 minutes, filter: this is the first extract. Warm the insoluble matters with more alcohol and filter again: this is the second extract. Repeat the extraction a third time. Keep the three extracts separate. Each should be evaporated at as low a temperature as possible, not exceeding 50° C., and preferably in a vacuum at the ordinary temperature, if this can be done fairly quickly. The syrupy residues must be treated with water and a drop of acetic acid, passed through wet filters to separate fat, rendered just alkaline with ammonia, and shaken with a moderate quantity of a mixture of equal volumes of ether and chloroform (Allen). By a stoppered funnel or burette the ethereal layer is separated, the shaking with ether and chloroform and the separation repeated a second and a third time, the ethereal extracts mixed, transferred to a large porcelain dish, and evaporated, first in a current of air, then in a vacuum or spontaneously. As the solvents evaporate, water generally appears: this hinders any crystallization. Therefore the residue must be rendered dry, then dissolved in a little anhydrous chloroform (dried by standing over fused calcium chloride), and again evaporated in air in a large watch glass. The residue will generally be crystalline under the microscope if any alkaloid be present. Dissolve again in chloroform, transfer to a graduated burette, make up to a convenient volume (say 10 cubic centimetres), and transfer a measured fraction to a number of watch glasses, reserving about one-fourth for any subsequent quantitative test that may be necessary. Allow the liquid in the watch glasses to spontaneously 2. Moisten the contents of the second watch glass with a little water and a trace of acetic acid, and apply through an incision in the skin of the back of a young frog. He should be kept as comfortable as possible and the symptoms observed. Strychnia readily produces tetanus in this animal; other poisons also have peculiar effects. Some observers have used mice, rabbits, or cats; in the Palmer trial it was observed that dogs were not employed because they were inconvenient and might bite! On the whole this so-called physiological test has been overrated, as it is hardly to be expected that an animal with its back cut and otherwise injured will not exhibit some symptoms; and all who have kept wild animals in confinement will know how soon they become, first almost convulsive from excitement, then finally sink into stupor and die. If necessary, any judge may grant a special licence to the experts in a trial to make experiments on animals, otherwise such cruelty is rendered penal by the Vivisection Act. 3. To the third watch glass, after the contents have been dissolved as before, a drop of a solution of iodine in potassium iodide is added. Nearly all alkaloids give a brown precipitate. If none occur, a negative conclusion may be expected. 4. Test the fourth watch glass in one corner for strychnia by concentrated sulphuric acid and peroxide of manganese; in another corner for morphia by iodic acid and starch; in a third corner for brucia (and morphia) by strong nitric acid. (See the special paragraphs on these reactions, pp. 280, 285.) 5. If there is still no indication, and no information has The second and third extractions of the organs must now be considered. Most of the text-books recommend that all the extracts should be mixed. The objection to this is, that since the alkaloid is usually present in very small amount, the first extraction will remove nearly all of it, while the second and third will mainly contain other matters, and therefore will be only adding to the impurities, and consequently to the difficulty of isolation. If it be worth while, the second and third extracts may be treated separately as above, and should any further quantity of alkaloid be found, it may be determined quantitatively, and the amount added to that already obtained. It has been proposed to precipitate the original spirituous extract by neutral or basic acetate of lead, which throws down many impurities, but leaves the alkaloids in solution. After filtration, the liquid is treated with a current of sulphuretted hydrogen to remove lead; again filtered, evaporated (as speedily as can be done without overheating) to a moderate bulk, and treated with a little ammonia and with ether-chloroform as before. If the sulphuretted hydrogen be left exposed to the air for some time, it oxidizes to sulphuric The foregoing process may fail to extract morphia, curarine, and solanine, as these, being very little soluble in ether-chloroform, may remain behind in the aqueous liquid. This, therefore, should be afterwards treated in one of the following ways:— 1. Heat some redistilled amylic alcohol nearly to boiling (it boils at 120° C.), add an equal volume to the aqueous (alkaline) solution; shake vigorously, separate while still hot, and shake again with a fresh, but rather smaller, quantity of the hot solvent. The united amylic alcohol solutions will contain all the morphia, but can only be distilled in vacuo, since at 120° C. the stability of the morphia would be endangered. It is better to extract the morphia from the amylic solution by shaking with successive small portions of weak acetic acid, separating each time, till the acidity remains unneutralized. The alkaloid will now be in the acid solution. Nearly neutralize this with ammonia, evaporate at a gentle heat, and apply the special tests. 2. Instead of the above, the aqueous alkaline solution may be agitated with a mixture of equal volumes of ether and pure acetic ether (the latter having been previously purified from free acid by standing over powdered carbonate of lime). Although this mixture does not extract the morphia so readily as amylic alcohol, it has this advantage that, after separation from the aqueous layer, it can be evaporated at a moderate temperature, when the morphia, if in sufficient quantity, will be left in the crystalline state, and can be tested as usual. If sufficient material be at hand, of course both processes may be used. Selmi (Gazz. Chim. Ital. vi., 32) has given a process for alkaloidal extraction of which I have no experience. When the alkaloid is obtained in a sufficiently pure form and in sufficient quantity, the sublimation process of Dr. Guy, as improved by Blyth, may be used. For the entire original method, see Blyth’s Practical Chemistry, page 285. Dr. Guy’s “subliming cell” is a ring of glass tubing about ?-inch long and ? to ½-inch diameter, ground true and smooth at top and bottom, resting on a circle of thin microscope glass, and covered with another similar circle. The alkaloid, thoroughly dry, is placed on the lower disc (a drop of the solution may be evaporated on it), the whole fitted together, and floated on mercury, or better, fusible metal, contained in a small glass beaker nearly full, supported on wire gauze over a small flame. A thermometer held by a clamp dips in the liquid metal. With a hand lens of as high power as possible, the melting point, and also the point when the first sublimate occurs on the upper glass, may be observed. As soon as the sublimate has become sufficiently distinct, the upper disc is removed, replaced by another, and examined under ¼-inch power of the microscope. The heat is slowly raised till charring occurs, and anything characteristic noted. Morphia gives a clouding, consisting of minute dots, at 150° C.; from 188° to 200° C., distinct crystals are obtained; then it commences to brown, melt, and carbonize. Strychnia gives a minute sublimate of fine needles at 169° C., and melts at about 221° C. Brucia melts at 151° C., browns easily, but gives no true sublimate. Aconitine or aconitia melts at 183° to 184° C. Pseudaconitine melts at 104° to 105° C., and easily decomposes, giving off water. Commercial aconitine usually melts below 100° C., and gives an amorphous sublimate above 150° C. The reactions of the other alkaloids will be found in Blyth’s Practical Chemistry. In order to avoid repetition, the mode of preparing the general reagents for alkaloids will be given here. 1. Mayers Reagent, potassio-iodide of mercury, already described (p. 7; Liebig’s Annalen, 133, 286), gives white precipitates with almost all alkaloids. The latter can be recovered from the precipitate by treating it with a solution of zinc chloride mixed with caustic soda. (Mayer.) 2. Potassium tri-iodide, a solution of iodine in potassium iodide, gives a brown or reddish precipitate. 3. Sonnenschein’s test, Phosphomolybdic acid, is prepared as follows. To a warm solution of molybdate of ammonia acidified with nitric acid, phosphate of soda is added as long as any yellow precipitate is obtained. The precipitate is washed with water containing a little nitric acid, and heated with sodium carbonate solution till dissolved. Evaporate to dryness, heat to expel ammonia, add a little nitric acid and heat again. One part of the residue is then dissolved in a mixture of one part of nitric acid of 1·4 sp. gr., and nine parts of water. With this reagent strychnia gives a pale, other alkaloids a bright yellow flocculent precipitate, in very dilute solutions. The precipitates are soluble in ammonia, with the production of a greenish blue colour in the cases of aconitia and morphia. From the alkaline liquid the alkaloid can be dissolved out by at once shaking with ether-chloroform or hot amylic alcohol as already described. Instead of using ammonia, the precipitate may be agitated with barium carbonate, which has less tendency to decompose the base on its liberation. 4. A solution of bismuth iodide in iodide of potassium is recommended by Dragendorff (Zeitschr. f. Chimie, 1866, 478). 80 grammes of commercial bismuth subnitrate are dissolved in 200 cubic centimetres of nitric acid of sp. gr. 1·18: 272 grammes of potassium iodide dissolved in a little water are added, the potassium nitrate allowed to crystallize 5. Scheibler has proposed Phosphotungstic acid as a precipitant. Sodium tungstate is digested with half its weight of phosphoric acid, sp. gr. 1·13: on standing, phosphotungstic acid crystallizes. Its solution is said to give a distinct precipitate with 1/200000 of a grain of strychnia and 1/100000 of quina, and with similar amounts of other alkaloids. From this precipitate the alkaloid is obtained by treating with sufficient milk of lime and shaking with ether-chloroform, &c., as before. He recommends the previous removal of impurities by lead acetate and sulphuretted hydrogen as already described (p. 7) (Fresenius, Zeitschr. f. anal. Chemie, 12, 315). 6. Picric acid, a saturated aqueous solution, gives precipitates in neutral solutions of morphia and atropia. In solutions acidified with sulphuric acid it gives the following:—morphia, and pseudomorphia, no precipitate; aconitia, a precipitate only in concentrated solutions; other alkaloids of opium, a thick precipitate. 7. Animal charcoal, previously purified by hydrochloric acid and thorough washing with water, when digested with neutral or alkaline solutions of alkaloids, not too dilute, absorbs them from the liquid. The charcoal, washed twice or thrice with small quantities of water, is dried at a moderate temperature, and boiled with strong alcohol, which extracts the alkaloid. This process has been used for separating picrotoxin from beer, but has the inconvenience that the alkaloid is liable to gradual oxidation within the pores of the charcoal, and that the separation is never complete. 8. All alkaloids form with platinic chloride double salts of more or less sparing solubility. These precipitates, washed, dried and weighed, and then burnt, leave metallic platinum, the amount of which yields a clue to the composition of the base. But aconitine and narcotine are only thrown down from concentrated solutions, and a few are not precipitated at all. Hence this test is of only occasional value in toxicological work. The same may be said of auric chloride. 9. Tannin or tannic acid, a moderately strong solution in water, throws down most alkaloids. Coffee and tea, and other tannin-containing infusions, have, therefore, been used as antidotes with dubious success. As a test it is not distinctive. 10. Phospho-antimonic acid (Schultze), prepared by mixing antimony pentachloride with ordinary sodium phosphate and decanting the clear liquid, gives whitish amorphous precipitates with alkaloids. 11. Silico-tungstic acid is prepared by boiling commercial tungstate of soda with fresh gelatinous silica. Filter and allow to crystallize. This gives precipitates with very dilute solutions of alkaloids, but it is also precipitated by ammonium chloride (Godefroy, Arch. d. Pharm., Nov. 1879). Zaubenheimer recommends it as a most delicate test: the precipitate may be decomposed by soda or potash, and the base extracted by ether-chloroform. 12. Auric chloride, palladious chloride, and mercuric chloride have been proposed, but are not of much use. Potassium chromate and sulphocyanide, and sodium nitroprusside give somewhat insoluble precipitates, generally crystalline and of characteristic appearance under the microscope. These tests should be strong, and must be used in small quantity. Ptomaines or Cadaveric Alkaloids.—Much attention has been attracted lately by the possible interference to toxicological detections owing to the undoubted existence of natural In an Italian criminal prosecution, F. Ciotto, who made the investigation of the corpse, gave it as his opinion that strychnia was probably present. Selmi, for the defence, pointed out differences from strychnia, and considered the compound to be a ptomaine. [Arch. Pharm. (3), 19, 187.] This will show the importance of the subject. Casali (Gazetta, 1881, 312) regards ptomaines as not true alkaloids, but as “acid or basic amidated compounds.” It is only the basic ones that will interfere with testing. Panum and Bergmann have isolated a substance called “sepsin,” generated by putrefaction, poisonous, acting like a ferment but not destroyed by boiling, soluble in water, but insoluble in alcohol, and thereby distinguished from alkaloids. Sonnenschein and Zuelzer found a product of putrefaction which produced tetanic symptoms, besides one resembling atropine. But these substances, or similar ones, can be produced without putrefaction, as Paterno and Spica have shown that fresh blood and fresh albumen (white of egg) yielded, with phosphomolybdic acid, potassio-mercuric iodide, and other alkaloidal reagents, precipitates like those of the vegetal alkaloids. Selmi has even supposed that death from various diseases may be due to the formation of these compounds. The same author obtained from a dead body one month after death a considerable amount Brouardel and Bouting (Compt. Rend. 92, 1056) propose the reducing action of ptomaines as a distinction between them and vegetal alkaloids. The solution in weak acid is added to a dilute mixture of ferric chloride and potassium ferricyanide: the latter, if a ptomaine be present, is reduced to ferrocyanide, and Prussian blue is thereby precipitated. But Spica (Gazetta, 11, 486) has shown that strychnia, brucia, morphia, and some others produce this reaction readily, and Beckurts (Arch. Pharm. 3, 20, 104) adds aconitine and others as producing it slowly. Hence the distinction is delusive. See also Husemann (Arch. Pharm. 3, 16, 169; also 3, 20, 270), Tauret (Compt. Rend. 92, 1163). The discovery of these bodies has certainly raised a new difficulty for toxicologists, and suggested a new and plausible defence, as it must be confessed that at present there is no general method of distinguishing between “cadaveric” and vegetal alkaloids. Yet this mainly affects the “physiological” tests—on frogs and other small animals—for there is no ptomaine yet discovered which gives all the reactions of strychnia, morphia, &c. If a chemist be asked, “Could any other substance produce these reactions?” he can only answer, “I do not know of any”; he cannot aver the impossibility. Then the circumstantial evidence must decide. In conclusion, the following principles should be noted:— 1. The quantity of poison found is generally only a small fraction of the quantity taken. The vomit and evacuations are frequently lost, and much may be decomposed by vital actions in the body, or by putrefaction. That which has caused death is probably thereby either decomposed or so combined as to be rendered undetectible: that which is found is merely the surplus beyond the fatal dose. This would account for the frequent non-discovery in the tissues when a small amount has been given, or much time has elapsed. To metallic poisons this does not apply, as, unless eliminated, they can always be found. See further under Strychnia. 2. The symptoms will differ according to the dose, the form (solid or solution, pure or admixed), habit, or idiosyncrasy, the state of health, &c. 3. In the post-mortem examination, appearances common to dead bodies generally are often mistaken for the effects of poison. See Casper’s Handbook, vol. I., et passim. 4. Unhealthy or improper food or acute disease may cause suspicious symptoms. This is the commonest solution of suspected poisoning. 5. In experiments on animals, it may be objected that they are inconclusive as to man. This is not strictly true. But if a recent vomit proves poisonous to an animal, with the same symptoms as in the man, that is almost conclusive evidence. 6. When a poison is not found by analysis, it does not follow that it has not caused death. Unequal distribution, uncertainty of tests, improper securing of the samples (Palmer case), decomposition or elimination of the poison, may hinder discovery. 7. In every case, if possible, the approximate quantity of the poison should be ascertained and stated. This specially applies to substances that may have been administered medicinally. “If poison be administered with intent to murder, it is not necessary that there should be enough in the article administered to cause death, or that it should be given in such a way as to act fatally. If any poison be there, and the intent be proved, the crime of attempting to administer poison is complete.” [Judge’s ruling in Hartley, Cent. Crim. Court, May 12th, 1850; Reg. v. Bacon, Lincoln Summer Assizes, 1857; Reg. v. Southgate, Chelmsford Lent Assizes; Reg. v. Cluderay, York, 1849]. For minute directions as to the conduct of toxicological investigations, see Taylor’s Medical Jurisprudence, 1873, I., 202-209; also Guy and Ferrier’s Forensic Medicine, 1881, p. 359, et seq. |