Determination of acidity constants at 37 °C through the internal standard capillary electrophoresis (IS-CE) method: internal standards and application to polyprotic drugs

This work provides the p K a at the biorelevant temperature of 37 °C for a set of compounds proposed as internal standards for the internal standard capillary electrophoresis (IS-CE) method. This is a high throughput method that allows the determination of the acidity constants of compounds in a sho...

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Bibliographic Details
Published in:Analyst (London) 2020-08, Vol.145 (17), p.5897-594
Main Authors: Lebanov, Leo, Fuguet, Elisabet, Melo, Javier M, Rosés, Martí
Format: Article
Language:English
Subjects:
Capillary electrophoresis
Drugs
Electrophoresis
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Summary:This work provides the p K a at the biorelevant temperature of 37 °C for a set of compounds proposed as internal standards for the internal standard capillary electrophoresis (IS-CE) method. This is a high throughput method that allows the determination of the acidity constants of compounds in a short time, avoiding the exact measurement of the pH of the buffers used. pH electrode calibration at 37 °C can be avoided too. In order to anchor the p K a values obtained through the IS-CE method in the pH scale, the acidity constant at 37 °C of some of the standards has been determined also by the reference potentiometric method. In general, a decrease in the p K a value is observed when changing the temperature from 25 to 37 °C, and the magnitude of the change depends on the nature of the compounds. Once the p K a values at 37 °C of the internal standards have been established, the method is applied to the determination of the acidity constants of seven polyprotic (5 diprotic and 2 triprotic) drugs. The obtained mobility-pH profiles show well-defined curves, and the fits provide precise p K a values. Due to the lack of reference data at 37 °C only the p K a values of labetalol can be compared to values from the literature, and a very good agreement is observed. This work provides the p K a at the biorelevant temperature of 37 °C for a set of compounds proposed as internal standards for the internal standard capillary electrophoresis method. The method is applied to p K a determination of polyprotic drugs.
ISSN:0003-2654
1364-5528
DOI:10.1039/d0an00918k