Mo?lher of the .'?~vedish p/lnrr?locopa'in Cor?ir??ission C1:KI'AIN glycosidcs of plant origin possess valuable cardiotonic propcrties. The Families Scrophulariaceae and Apocynaceae are the plant orders which contain most members furnishing drugs of therapeutic ulue. If in this connection the toad poisons are included, the heartactive substances from n chemical viewpoint may be subdivided into three large groups : the digitalis-strophanthus group, the scilla-helleborus group and thc nitrogenous venoms secreted by the parotid glands of toads. The chief ditferences between the groups are: the members of the first group are glycosides, the aglucones of which contain a fivemembered lactone ring, the members of the second group are glycosides, the aglucones of which contain a six-membered lactone ring and the members of the last group are suberylarginine derivatives of acetylated hydroxylactones more closely related to the scilla group than to the digitalis group.Only the first group will be discussed here. The ring system of the cardiac glycosides from the genera Digitalis and Sfrophcrnthits is given below: --

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SINCE Eulerl in 1946 demonstrated the important role played by (-)-noradrenaline (I) as a transmitter of adrenergic nerve impulses and later isolated it in pure form from the adrenal medulla2, this substance has found a wide clinical application. Exerting an overall vasoconstrictor effect, it is used, for instance, to maintain the blood pressure in surgical and traumatic shock and other acute hypotensive states. Because of its greater stability to oxidation it is progressively supplanting adrenaline in many instances, e.g. as a vasoconstrictor in injectable local anaesthetics, as a haemostatic and so on3. Tullar and c o -~o r k e r s~?~ have discussed the substance from different points of view.Noradrenaline is used mainly as the laevo-isomer, usually as the hydrochloride or the bitartrate, this isomer being about twice as active' as the racemic form. Several solutions containing the equivalent of 0.1 per cent. of (-)-noradrenaline are commercially available, but there is contemplated for inclusion in the Swedish Pharmacopceia a solution containing only 0.001 per cent. of noradrenaline as the bitartrate.For the chemical estimation of noradrenaline in solution one may utilise, with slight modifications, several methods originally intended for the determination of adrenaline, e.g. the adrenochrome methods and our fluorescence method with strong alkali. Moreover the absorption peak at 279 mp in the ultra-violet spectrum offers a possibility for the quantitative determination of noradrenaline, E: being 85.0 for a solution of 0.01 N hydrochloricacid in this laboratory. Thecondensation of the primary aliphatic amine moiety with a carbonyl compound implies a selective method', being capable of determining noradrenaline even in adrenaline.The solutions containing 0.1 per cent. of noradrenaline may be conveniently assayed by the methods mentioned, but in the case of the 0.001 per cent. solution only the fluorescence method seems to have a sufficient sensitivity. As noted by EhrlCn* and others, a drawback of the fluorescence method for adrenaline is the instability of the fluorescence. A great improvement was made, however, in 1949, when Natelson et aL9 introduced a method for the determination of adrenergic amines in blood involving oxidation and condensation in alkaline medium with a primary aliphatic amine. As proposed by Weil-Malherbe and Bonelo ethylene diamine may be employed as the amine, thus by cyclisation producing a fairly stable fluorescent compound (formula 111, below). However, this method does not work in the presence of pyrosulphite, a serious limitation to its usefulness, because noradrenaline solutions generally are stabilised with pyrosulphite.

THE current interest in isonicotinic acid hydrazide has prompted the need for a rapid assay method. It is well known that hydrazines in slightly alkaline solutions are oxidised by iodine according to the scheme :-Mono-acylhydrazides are said to behave in a different way1 :-However, isonicotinic acid hydrazide consumes 4 equivalents of iodine when oxidised as described below. Thus the mechanism of the reaction seems to be analogous to that of hydrazines.Isonicotinic acid hydrazide may be titrated in the following manner :-Dissolve 50 mg. of the substance in 50 ml. of water, add 1 g. of sodium bicarbonate and 25 ml. of 0.1N iodine. Allow to stand for 15 minutes. Cautiously add 10 ml. of 5N hydrochloric acid and titrate the excess of iodine with 0: 1N sodium thiosulphate using starch solution as indicator. 1 ml. of 0-1N iodine corresponds to 0.003429 g. of C,H,ON,.Two samples of the hydrazide from different manufacturers, m.pt. 168" to 169" C. and 170" to 171" C. (Kofler), assayed 97.8,97.8,98.0 and 98.4, 98.6, 98.7, 98.2 per cent.Commercial tablets containing 50 mg. of the hydrazide were analysed in a similar way, the only difference being that the suspension of the tablet powder was centrifuged before the addition of the sodium bicarbonate. The following results were obtained :--47.7, 48.1, 48.3 and 48.2 mg. per tablet.

A modification of the fluorimetric method for the determination of adrenaline and noradrenaline in pharmaceutical solutions is described. In this method sulphite present is destroyed with iodine, the added excess of which is reduced with arsenous acid, a manipulation which does not affect the fluorescence obtainable.ADRENALINE and noradrenaline in low concentrations are most suitably determined by the fluorimetric method1#2. In pharmaceutical solutions, sulphite is usually present as a stabiliser. This introduces a difficulty in the determination of the catechols as these cannot be quantitatively transformed into the corresponding adrenochromes by potassium ferricyanide or by manganese dioxide if the sulphite present is not destroyed before the oxidation of the catechols.Adrenaline, however, can be determined ad modum EhrlCn3, even in the presence of sulphite by measuring the transient fluorescence obtained by oxidation with air in strongly alkaline solution. In this procedure there seems to be no interaction between the adrenochrome formed and the sulphite. A possible explanation of this phenomenon is that this reaction is performed at such a high pH that all sulphite is present as S O 3 --being non-reactive, while the oxidation with MnO, or Fe(CN), ---is performed in neutral or slightly acid solution, where the sulphite is present partly as HS0,-which is reactive forming a bisulphite compound with the adrenochromes.Noradrenaline cannot effectively be determined by the method of EhrlCn3 as the sensitivity is much lower than for adrenaline. It is, therefore, necessary first to oxidise noradrenaline with ferricyanide or MnO, to noradrenochrome and then to transform it with sodium hydroxide to the fluorescent adrenolutine. This procedure may sometimes be preferable in the determination of adrenaline as a higher fluorescent energy is obtained.As mentioned before, the sulphite present has to be destroyed in such a way that the fluorescence obtained is not affected. Several methods described are based on the separation of the catechols from the sulphite or on the destruction of the latter. The separation methods are tedious and not well suited to routine work. The destruction of the sulphite ions is usually brought about by oxidation with iodine in an acid solution such that the reaction between iodine and the catechols proceeds very slowly. The excess of iodine added has to be removed in order not to suppress the fluorescence later on. This can be done by addition of thiosulphate, an excess of which, however, also has a strong quenching influence on the fluorescence. The influence of thiosulphate is rather peculiar ; added to a solution of the adrenochrome it has no influence on 764