AUTOMATED ANALYTICAL SYSTEMS FOR DRUG DEVELOPMENT STUDIES .1. A SYSTEM FOR THE DETERMINATION OF DRUG STABILITY

An automated system consisting of a pH-stat, microdialysis sampling an d a liquid chromatograph was assembled to measure the rate of rapid ch emical reactions. 2',3',5'-Triacetyl-6-azauridine was used as a model compound to validate the performance of the automated system. Buffer c atalysis was minimized by using a non-catalytic concentration of berat e buffer along with a pH-stat to maintain the pH during the kinetic ru n. The microdialysis sampling technique permitted sample quenching and buffering of the solutions to a pH compatible with the LC column mate rials. The combination of microdialysis sampling and rapid LC analysis allowed reactions with a half-life of approximately 1 min to be sampl ed every 30 s. The rates of hydrolysis of the drug, measured at differ ent conditions of temperature (37-70 degrees C) and pH (9.0-10.5) usin g the automated system, compared well with the previously determined v alues.