Automated analytical systems for drug development studies. I--A system for the determination of drug stability.
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.
Shah
K P
KP
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
Zhou
J
J
Lee
R
R
Schowen
R L
RL
Elsbernd
R
R
Ault
J M
JM
Stobaugh
J F
JF
Slavik
M
M
Riley
C M
CM
D001322:Autoanalysis / Q000295:instrumentation; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002853:Chromatography, Liquid; D004355:Drug Stability; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D017551:Microdialysis; D008956:Models, Chemical; D013696:Temperature