Early work in the development of liquid-liquid separation techniques was undertaken by Cornish et al. with a process called "systematic fractional distribution" as well as Randall and Longtin, however, the central figure is certainly Lyman C. Craig. Lyman Craigs development of countercurrent distribution began with studying the distribution of a pharmaceutical, mepacrine (atabrine), between the two layers of an ethylene dichloride, methanol, and aqueous buffer biphasic solvent system. The distribution coefficient (K which coincides with partition coefficient) of atabrine varied by the composition of the solvent system and the pH of the buffer. In the next article, Craig was inspired by the work of Martin and Synge with partition chromatography to develop an apparatus that would separate compounds based on their distribution constant (K which coincides with partition coefficient). It was shown that a solvent system composed of benzene, n'-hexane, methanol and water would separate mixtures of organic acids. It is remarkable that the mathematical theory developed hand-in-hand with the progression of applications. Craig continued to pursue this method of separation by testing different compounds, formulating biphasic solvent systems, and most importantly developing a commercially viable instrument.
The CCD technique was employed in many notable separations such as penicillin, polycyclic aromatic hydrocarbons, insulin, bile acids, ribonucleic acids, taxol, Streptomyces antibiotics. and many other antibiotics.