amorphous quinine, the medicine will answer the test of the Pharmacopoeia. This substitution can, however, easily be detected by transforming the separated quinine into a neutral oxalate. This oxalate after being thoroughly dried on a water-bath is dissolved in chloroform, and the solution, if necessary, filtered. If a few drops of water are put on the top of this solution in a test tube, the oxalate of quinine will take a part of the water, and crystals of oxalate of quinine will appear in the chloroform, whilst the water on the top remains clear and uncoloured if the medicine is not sophisticated. If it contains, however, amorphous quinine, the oxalate of this base will be taken up from the solution in chloroform, and the water on the top of this solution will be more or less yellow-coloured by the oxalate of amorphous quinine which has been dissolved by the

water.

The PRESIDENT said this was a practical and useful test, which must commend itself to notice.

Mr. UMNEY thought the test put forward by Dr. de Vrij seemed simple and elegant, and might prove valuable. There could be no question that amorphous quinine was always to be found in the citrate of iron and quinine to some certain extent, and there could also be no doubt that the alkaloid was converted from the crystallizable into the amorphous state during the process of manufacture, but this only occurred to a small extent, and if pure crystalline sulphate of quinine were used, this change would be very slight. He looked upon this test as one which was very simple, and could be applied by almost any one. It was known how insoluble oxalate of quinine was, and the paper showed that the oxalate of amorphous quinine was soluble in water.

Mr. FLETCHER said he hoped when he saw the title of the paper that the test proposed by Dr. de Vrij would have been a quantita tive, instead of, as it appeared, a qualitative one. As Mr. Umney had said, amorphous quinine might be found in any sample of citrate of iron and quinine, and if the Pharmacopoeia process were strictly followed, he would undertake to say that at least one-fourth of the quinine would be converted into the amorphous condition, the heat employed in evaporating the solution to a syrupy consistence being quite sufficient to convert a large proportion of the crystallizable quinine into the amorphous state, as he had found by practical experience. In the paper he read at the last meeting of the Conference, he described a process for the estimation of quinine in the citrate of iron and quinine, which was based on the fact that

when the alkaloid was obtained, as in the usual way, by precipitation with ammonia and re-solution in ether, evaporating the ether, and weighing the anhydrous quinine (dried at 120°), one was able to calculate exactly how much sulphuric acid was required to convert that quinine into basic sulphate, and if the requisite number of cubic centimetres of decinormal sulphuric acid were added to this anhydrous quinine, and the vessel in which it was contained were kept for a short time at a gentle heat, the whole of the quinine would be converted into basic sulphate, which crystallized out on cooling. Further experience, however, had convinced him that i was not advisable to dry the quinine at 120°, because at that temperature a very considerable portion of it was converted into amorphous quinine. He had made a number of experiments to verify this, by taking pure sulphate of quinine-not that of commercebut that which had been freed from cinchonidine by five recrystallizations. Taking a weighed quantity of this sulphate, precipitating by ammonia, extracting by ether, and drying at 120°, and reconverting that into sulphate by the addition of the requisite number of cubic centimetres of decinormal sulphuric acid, there was a loss of from 5 to 10 per cent. on the theoretical quantity. Not only that, but if the filtered solution from the first crystallization of the sulphate were examined, it would be found that a large quantity of the quinine which was missing as crystallizable sulphate was present in the solution as amorphous quinine, as could be easily proved by precipitating with ammonia, redissolving in ether, and drying that at 120°, when the precipitate, instead of being white, as in the first instance, would be quite yellow, and it would have precisely the taste of amorphous quinine. He thought Dr. de Vrij's process would very possibly condemn as sophisticated citrate of iron and quinine which had been prepared according to the British Pharmacopoeia process, and the more strictly that process was followed, the more amorphous quinine would be produced. There was a very simple test, which every pharmacist could use for himself with a very little practice, and which would detect 5 per cent. of amorphous quinine. It was simply necessary to take a scale and place it on the tongue, the difference in taste between that and the genuine preparation would be so distinct that no one could possibly mistake it. The bitter was as distinct as was the bitter of aloes from that of quassia. From experiments he had made, he had conclusively proved that there was no better test for the presence of amorphous quinine than this.

Professor ATTFIELD suggested that possibly Dr. de Vrij's process

might be made quantitative by treatment of the aqueous solution, evaporation, and so on.

Dr. SENIER said it seemed to him that although in the hands of experienced chemists this process might be useful, in the hands of ordinary pharmacists, or those who had not had special training in the crystallization of these salts, it would be found difficult. One portion of the process involved the formation of neutral oxalate from a certain amount of possibly mixed alkaloid, but that amount was not mentioned. It would be necessary to use several grams at least, of citrate of iron and quinine, and then it would not be found easy to neutralize the alkaloid, so as to secure practically complete crystallization. He should like to ask Mr. Fletcher a question in respect to the crystallization of neutral sulphate of quinine from the residue of mixed alkaloid obtained from commercial citrate of iron and quinine. In his paper of last year, Mr. Fletcher recommended that to convert this residue into neutral sulphate it was only necessary to treat it with an amount of decinormal sulphuric acid, measured from a burette, which would correspond to the weight of alkaloid were it all quinine. Had Mr. Fletcher found no difficulty in carrying out this method? He (Dr. Senier) had found that much care was necessary in order to convert quinine into neutral sulphate. Indeed, he should have said, on the face of it, that any measurement of a decinormal solution of sulphuric acid from a burette would not have been accurate enough. He would suggest also whether the amorphous quinine derived from white crystallized sulphate of quinine would necessarily be coloured.

Mr. FLETCHER said he recommended in this test 20 grams of sulphate to be used for the examination. From that amount there was a very fair proportion of quinia obtained, and if the decinormal solution of sulphuric acid was made carefully, and tested gravimetrically, there could not possibly be any more accurate method. Certainly it was much more accurate than deciding whether one had enough sulphuric acid to convert the alkaloid into basic sulphate by testing with litmus. As far as his own experience went, the quantity of sulphuric acid theoretically indicated had been found absolutely correct. The whole of the alkaloid went into solution, a perfectly transparent solution was obtained, which was alkaline to litmus, and from this solution the basic sulphate crystallized out in splendid crystals. With regard to the second question, he certainly should expect that the amorphous alkaloid would be slightly coloured, because he believed that it was always so, however pure or however prepared. He thought the colour

combined with taste was as good an indication of the presence of amorphous quinine as could be obtained, provided it had been extracted by ether, and dried at 120°.

Mr. NAYLOR said he had made a great number of quantitative estimations of quinine by Mr. Fletcher's process, and always found it answer admirably, nor had he met with the difficulty of neutralizing the quinine to which Dr. Senier had referred. Altogether the process appeared a very manageable one and exceedingly satisfactory. He preferred it much to the method of dissolving the quinine in sulphuric acid, and ascertaining when the solution was neutral by means of litmus, or by afterwards making it neutral by means of alkali, so as to obtain the basic sulphate. Different samples of citrate of iron and quinine differed very greatly in their acidity, and he should like to ask whether it would not be possible to get scales which were much more neutral than those generally sold in the market. Some makers prepared the citrate far less acid than others, but he did not know whether the presence of amorphous quinine exercised any influence on this.

Mr. FLETCHER said the citrate of iron and quinine which he found most appreciated by pharmacists was that which dissolved readily without any deposit; but such citrate contained much more citrate of ammonia than the Pharmacopoeia preparation. A short time ago a wholesale house applied to him for an explanation of a reaction which had been pointed out to them by a chemist in the country, as occurring when dispensing citrate of iron and quinine with iodide of potassium. A large precipitate occurred slightly coloured, which caused the mixture to be returned with the remark that the pharmacist who had previously dispensed it had supplied a mixture perfectly clear and bright. On examining the citrate of iron and quinine which had been supplied, he found it in all respects perfectly pure, but it was rather slow in dissolving, from which he inferred that the citrate of ammonia was somewhat deficient. He tested a sample of Howard's citrate of iron and quinine with iodide of potassium, and found that it gave a precipitate, which was no doubt hydriodate of quinine, and its colour and quantity would be dependent on the one hand on the acidity of the citrate of iron and quinine, and on the other on the alkalinity of the iodide of potassium. As he had said, the citrate which was most appreciated contained an excess of citric acid and citrate of ammonia, and a preparation of that sort he found would not give a precipitate immediately with iodide of potassium.

Mr. GERRARD said Dr. de Vrij's paper pointed out a defect in

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citrate of iron and quinine with which few were previously ac quainted, and one practical result would perhaps be to try and remedy that defect. One of the best ways of doing so would be to dispense only a solution of citrate of iron and quinine which had not been submitted to the amount of heat required to get it into the scale form.

Mr. GREENISH observed that in dispensing iodide of potassium in a mixture of citrate of iron and quinine there was occasionally a separation, but he had always considered it was hydriodate of quinine formed, and did not think it was influenced by the solution, because he had used it both in solution and not in solution.

Mr. GERRARD said it was the drying which produced the amorphous alkaloid.

Mr. HUGHES said he had found some difficulty in dispensing iodide of potassium with quinine, and if any one could suggest a means of overcoming it he should be very grateful.

Mr. FLETCHER said if the citrate of iron and quinine dissolved rather slowly, and did not form an absolutely brilliant solution, one might at once come to the conclusion that it was somewhat deficient in citrate of ammonia, and he should add either a little excess of citric acid or a solution of citrate of ammonia containing an excess of citric acid.

Mr. HOWELL Said Dr. Langdon Down frequently ordered citrate of iron and quinine with iodide of potassium, to which he generally added a small quantity of citric acid. When the prescription was in that form it ceased to precipitate.

Mr. GREENISH thought Mr. Fletcher's remark really opened a very grave question, whether a dispenser was justified in adding such a thing as citric acid with a view of obviating a decomposition which must occur in more or less time. He did not think he was.

Dr. SYMES could not endorse that view. He was the last to tamper unduly with a prescription, but as they had heard that day, citrate of iron as found in the market was not a definite chemical substance which could neither be more acid nor more alkaline than originally intended, but in fact was received in all sorts of conditions. One of his earliest difficulties as a dispenser was to dispense a prescription often written by an eminent physician at Leamington, containing a small quantity of sal volatile with citrate of iron and quinine. They found that with the article of one manufacturer, when manipulated properly, dissolving it first in a large bulk of water and using an acid citrate of iron and quinine, the mixture could be kept from depositing to any extent. In the case