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 minimiz...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 1994-08, Vol.12 (8), p.993-1001
Main Authors: Shah, K.P., Zhou, J., Lee, R., Schowen, R.L., Elsbernd, R., Ault, J.M., Stobaugh, J.F., Slavik, M., Riley, C.M.
Format: Article
Language:English
Subjects:
2′,3′,5-triacetyl-6-azauridine
Analysis
Autoanalysis - instrumentation
Automation
Biological and medical sciences
Chemistry, Pharmaceutical - methods
Chromatography, Liquid
Drug Stability
ester hydrolysis
General pharmacology
Half-Life
Hydrogen-Ion Concentration
Hydrolysis
Kinetics
liquid chromatography
Medical sciences
Microdialysis
Models, Chemical
Pharmacology. Drug treatments
Temperature
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Summary: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°C) and pH (9.0–10.5) using the automated system, compared well with the previously determined values.
ISSN:0731-7085
1873-264X
DOI:10.1016/0731-7085(94)E0011-O