Journal
JOURNAL OF CHROMATOGRAPHY A
Volume 1218, Issue 25, Pages 3928-3934Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.chroma.2011.04.054
Keywords
pK(a); Acidity constant; Capillary electrophoresis; Internal standard; High throughput method
Funding
- Ministerio de Educacion y Ciencia of the Spanish Government
- Fondo Europeo de Desarrollo Regional of the European Union [CTQ2007-61608/BQU]
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A set of 25 monoprotic bases is proposed as internal standards for pK(a) determination by capillary electrophoresis. The pK(a) of the bases is determined and compared with available literature data. The capillary electrophoresis internal standard method offers numerous advantages over other typical methods for pK(a) determination, especially of analysis time and buffer preparation. However, it requires disposing of appropriate standards with reference pK(a) value. The set of bases established in this work together with the set of acids previously established provide a reference set of compounds with well-determined acidity constants that facilitate the process of selecting appropriate internal standards for fast pK(a) determination by capillary electrophoresis in high throughput screening of pharmaceutical drugs. In addition, the performance of the method when acidic internal standards are used for the determination of acidity constants of basic internal standards has also been tested. Although higher errors may be expected in this case, good agreement is observed between determined and literature values. These results indicate that in most cases structural similarity between the analyte and the internal standard might not be an essential requirement in the internal standard method. (C) 2011 Elsevier B.V. All rights reserved.
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