Robert A. Hatcher

A method for the quantitative determination of small amounts of quinin and quinidin with bromin water

We undertook to learn whether quinin could be determined quantitatively in extracts of animal tissues by means of the so-called thalleioquin color reaction, but it soon became apparent that the intensity of the color varies with too many factors to permit of its use for this purpose. It was observed, however, that the color of the bromin water disappeared sharply on the addition of a slight excess of quinin, and the present method depends upon the fact that when quinin is added to bromin they combine in definite proportions with the loss of the color of the bromin in reflected light. Hart 1 attempted unsuccessfully to estimate quinin quantitatively by means of the thalleioquin reaction. He found, however, that four atoms of bromin are absorbed by the quinin, two of them loosely. He says, “It follows, then, that quinine may be determined from its bromine absorption for five minutes in the manner stated: 1 cc. N/10 Br. = 0.0081 g. quinine.” This method has not been employed hitherto so far as we know. Nine solutions of quinin, varying widely in concentration and containing from 0.5 to 2.0 milligrams of quinin base, were prepared by one of us (H) and examined by the other (W), who did not know the strength of the solution in any case. The determinations were made with an average error of about five per cent. The necessary reagents are prepared in the following manner: Bromin water: Place a convenient volume of bromin in a bottle with a tightly fitting glass stopper, add water, and shake until saturation occurs with an excess of bromin in the bottom of the bottle. It keeps indefinitely. Diluted bromin water : Dilute a convenient volume of bromin water with nine volumes of water immediately before using.

Preliminary report on the behavior of certain local anesthetics

The fatal intravenous dose of each of the several substitutes for cocain varies enormously with differences in the rates of injection. Five or more times the fatal dose for sudden injection can be given in a period of one to two hours without causing death. The subcutaneous doses show even wider variations among the different drugs than the intravenous doses. All of the local anesthetics tested, including cocain, are mutually and quantitatively synergistic. They are all synergistic with epinephrin in its effect upon the blood pressure in a manner analogous to cocain. The systemic toxic actions of all of the members of the group are very closely alike and all cause death in cats by combined paralysis of the heart and respiratory center. Three of the members of the group-procain, stovain and apothesine-have been shown to be destroyed rapidly by the liver. All of the others are rapidly destroyed in the animal body, excepting cocain, and it seems probable that this destruction also takes place in the liver. Artificial respiration alone, or combined with cardiac massage, does not suffice to permit recovery from the sudden intravenous injection of 125 per cent. of the fatal dose of any of the local anesthetics. Artificial respiration and cardiac massage, combined with the intravenous injection of epinephrin, permit recovery in most cases from 125 to 150 per cent. or more of the fatal vein dose of all of the local anesthetics. The previous administration of ouabain permits recovery from 150 per cent. of the fatal dose of procain when artificial respiration is employed and the similarity in actions of all of the drugs leads one to suppose that it holds true of the other members of the group.