The Determination of Morphine.*

The estimation of morphine in biological material is difficult and tedious. Many methods have been advocated, not one of which has received the approval of successful employment by a considerable number of investigators. In the preliminary stages of projected work upon the behavior of morphine in the metabolism, it was necessary to subject existing methods to critical study for the purpose of identifying, and if possible of correcting, their inherent defects. It is too much to hope that a method for morphine shall be developed as reliable as those for inorganic substances; but it should be possible to discover what features in existing methods are most apt to give loss or contamination, and also to introduce some means of testing the reliability of an estimation after it has been made. The result of our work has been the selective elaborations of a series of methods for various classes of materials, which avoid such pitfalls as we have recognized, and with which we have secured satisfactorily consistent and reliable results. All methods for determining morphine consist of two parts: first, isolation of the alkaloid in a state of relative purity; second, measurement of its amount. In the early work on the qualitative recognition of morphine, suggestions are to be found upon which later quantitative methods have been built. Thus Lassaigne (1) removed the alkaloid by extraction in alcohol, and purified it by lead precipitations. The two classical procedures of Stas-Otto and Dragendorf include preliminary purification by the successive use of dilute acid and acid-