A fast high throughput method for the determination of acidity constants by capillary electrophoresis. 3. Basic...

Area of Science:

• Analytical Chemistry
• Physical Chemistry

Background:

• Accurate determination of acid-base dissociation constants (pK(a)) is crucial for pharmaceutical drug development and screening.
• Capillary electrophoresis (CE) offers advantages in speed and efficiency for pK(a) determination.
• The availability of reliable internal standards is essential for the accuracy of the CE method.

Purpose of the Study:

• To propose and validate a set of 25 monoprotic bases as internal standards for pK(a) determination by CE.
• To compare the determined pK(a) values with literature data.
• To evaluate the suitability of using acidic internal standards for determining the pK(a) of basic compounds.

Main Methods:

• Capillary electrophoresis was employed for pK(a) determination.
• A set of 25 monoprotic bases was utilized as internal standards.
• The performance of acidic internal standards for basic analyte pK(a) determination was assessed.

Main Results:

• The pK(a) values for the 25 proposed bases were successfully determined and compared with literature data.
• The CE internal standard method demonstrated advantages in analysis time and buffer preparation.
• Good agreement was observed between determined and literature pK(a) values, even when using structurally dissimilar internal standards.

Conclusions:

• The established set of monoprotic bases serves as a valuable reference for selecting internal standards in CE-based pK(a) determination.
• The CE internal standard method facilitates rapid pK(a) determination, particularly for high-throughput screening in drug discovery.
• Structural similarity between analyte and internal standard may not be a critical requirement for accurate pK(a) determination using the CE internal standard method.