T.HE ANALYST. APRIL, 1896. NOT13 ON THE TITRATION OF QUININE. By ALFRED H. ALLEN. (Read at the Meeting, Pebrunry 5, 1896.) IN titrating alkaloids much depends on the indicator employed and the method of applying it. Methyl-orange, rosolic acid, iodeosin, phloxin, phenol-phthaleh, gallein, lacmoid, brazil-wood, logwood, litmus, and cochineal have all been employed and have found advocates. The behaviour of the alkaloids and organic bases with indicators of neutrality has been very imperfectly studied. I t is frequently stated that a certain alkaloid is distinctly alkaline (presumably to litmus), but it is only rarely and of recent years that chemists appear to have attempted to estimate alkaloids by titration with standard acid. Litmus answers in some cases, but by no means invariably.With methyl-orange, in the majority of cases a determination of tolerable accuracy and a fairly sharp end- Where this is desired, phenol-phthalein is quite inapplicable.86 THE ANALYST. reaction are obtainable. Cochineal, brazil-wood, and logwood are often useful indicators. In titrating quinine, an anomaly occurs which has misled more than one observer. This arises from the fact that the ordinary quinine sulphate of commerce, having, when anhydrous, the formula (C,,H,,N,O,),,H,SO,, though practically neutral to brizzil-wood, logwood, and cochineal, is strongly alkaline to methyl-orange. The point of neutrality when titrating qginine with cochineal, braxil-wood, or logwood, is therefore reached when sufficient acid has been added to convert the quinine into the sparingly soluble sulphate of the formula Qu,,H,SO, ; whereas in the case of methyl- orange the end-reaction corresponds to the formation of the readily soluble acid sulphate of the formula Qu,H,SO,.Hence twice the volume of standard acid will be required by a given weight of quinine when methyl-orange is employed, as when brazil-wood, logwood, or cochineal is used as the indicator. If nitric acid or hydro- chloric acid be substituted for sulphuric acid, the results are similar, the salts Qu,2HN03 and Qu,2HC1 being neutral to methyl-orange. The sparingly-soluble sulphate, Qu2,H2SO4, is distinctly alkaline to litmus, and hence this indicator cannot be conveniently used for the titration of quinine, though the end-reaction is well marked. The fact that Qu,H,SO, is neutral to brazil-wood, and QuH,SO, to niethyl- orange, is parallel to many other instances, the most interesting being that of the phosphates of sodium. Thus : NaH,PO, is neutral to methyl-orange.Na,HPO, is neutral to phenol-phthalein. Na,PO, is neutral to “ Poirrier’s blue, C.L.B.” The foregoing statements are a record of facts observed independently in my laboratory, and carefully verified by numerous experiments. The main fact, how- ever, was previously recorded by Seaton and Richmond (ANALYST, xv. 43), who state that they ‘‘ found that quinine bisulphate is neutral to methyl-orange, while the base itself has no action on phenol-phthalein,” and they based on these facts a process for the determination of quiuine in medicines. Their instructions assume that the medicine originally contained excess of acid, and was free from any inorganic base precipitable by baryta.Seaton and Richmond give figures showing that the method is fairly accurate when applied to pure sulphate of quinine, but the conditions under which the titrations are performed in practice render the method of little value. I t is useless in presence of citric and other organic acids, and the colouring matter present in quinine wine prevents the end of the reaction from being accurately observed. Owing to no formula for ‘‘ quinine bisulphate ” being given by Seaton and Rich- mond, nor the consequences pointed out, the fact on which their process was based was misinterpreted by me (‘‘ Commercial Organic Analysis,’’ vol. iii., part ii., p. 403, footnote), and apparently has been quite overlooked by other writers. Nxperiments made in my laboratory on the titration of cinchonine and ciuchoni- dine with various indicators had led to such anomalous results as to render it doubtful if the constitution of these bases, or at least the composition of the com- mercial article, is correctly understood.THE ANALYST. My thanks are due to Mr. A. B. Searle for the referred to in this note. DISCUSSION. The PRESIDENT said that Mr. Allen had stated The facts as to the titration of the quinine alkaloids. 87 execution of the experiments \‘erg clearly and concisely the parallel drawn between quinine compounds and phosphates was especially interesting. I t was easy to understand how readily errors might be made in quinine estimations, in consequence of the nomenclature of the quinine salts. A similar instance of ambiguity had occurred in the case of the two chlorides of mercury.