Automated analytical systems for drug development studies. I--A system for the determination of drug stability

J Pharm Biomed Anal. 1994 Aug;12(8):993-1001. doi: 10.1016/0731-7085(94)e0011-o.

Abstract

An automated system consisting of a pH-stat, microdialysis sampling and a liquid chromatograph was assembled to measure the rate of rapid chemical reactions. 2',3',5'-Triacetyl-6-azauridine was used as a model compound to validate the performance of the automated system. Buffer catalysis was minimized by using a non-catalytic concentration of borate buffer along with a pH-stat to maintain the pH during the kinetic run. The microdialysis sampling technique permitted sample quenching and buffering of the solutions to a pH compatible with the LC column materials. The combination of microdialysis sampling and rapid LC analysis allowed reactions with a half-life of approximately 1 min to be sampled every 30 s. The rates of hydrolysis of the drug, measured at different conditions of temperature (37-70 degrees C) and pH (9.0-10.5) using the automated system, compared well with the previously determined values.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoanalysis / instrumentation
  • Chemistry, Pharmaceutical / methods*
  • Chromatography, Liquid
  • Drug Stability*
  • Half-Life
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Kinetics
  • Microdialysis
  • Models, Chemical
  • Temperature