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Issue 17, 2020
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Determination of acidity constants at 37 °C through the internal standard capillary electrophoresis (IS-CE) method: internal standards and application to polyprotic drugs

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Abstract

This work provides the pKa 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 pKa 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 pKa 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 pKa 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 pKa values. Due to the lack of reference data at 37 °C only the pKa values of labetalol can be compared to values from the literature, and a very good agreement is observed.

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

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Article information


Submitted
07 May 2020
Accepted
25 Jun 2020
First published
29 Jun 2020

Analyst, 2020,145, 5897-5904
Article type
Paper

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

L. Lebanov, E. Fuguet, J. M. Melo and M. Rosés, Analyst, 2020, 145, 5897
DOI: 10.1039/D0AN00918K

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