Early adventures in drug metabolism: 1. Role of the Bratton-Marshall reagent.

The Bratton-Marshall reagent is one of the real land-marks in the development of drug metabolism and pharmacokinetics, coming at a time when highly sensitive and specific analytical procedures were desperately needed for the measurement of drug concentrations in the body. Examples of its applications are taken from early work in the mid-40's and 50's in the Parke-Davis Research Laboratories, extending from primary aromatic amines (e.g., sulfonamides), to p-nitrophenyl compounds that must first be reduced to amines (e.g., chloramphenicol), and to phenyl derivatives that must be nitrated on a microgram scale and then reduced to aryl amines (e.g., phenytoin). The development and use of separation techniques such as liquid/liquid counter-current partition and paper chromatography is described. Emphasis is placed upon continued, progressive improvement in the basic assay procedures over long periods of time.