<abstract xmlns="http://www.w3.org/1999/xhtml"><p>A new method for determination of distribution coefficient of drugs azathioprine, 6-mercaptopurine and 6-thioguanine and nutrient folic acid used in the treatment of inflammatory bowel disease based on a miniaturized shake-flask and HPLC/DAD was developed. Special attention was made to the most commonly reported problems in the measurement of distribution coefficients using a shake-flask method such as mixing technique, speed and time, the temperature of experiment, type of buffer and its pH as well as <italic>n</italic>-octanol/buffer phase ratio. The concentration of compounds in the buffer is determined by HPLC directly from shake flasks or conventional 2-mL vials. The developed method was fully validated according to ICH guidelines. Furthermore, experimental data were successfully compared with lipophilicity and human intestinal absorption calculated by the use of four different theoretical approaches. The method shows potential for high-throughput measurements of a large number of compounds.</p></abstract>

A new method for determination of distribution coefficient of drugs azathioprine, 6-mercaptopurine and 6-thioguanine and nutrient folic acid used in the treatment of inflammatory bowel disease based on a miniaturized shake-flask and HPLC/DAD was developed. Special attention was made to the most commonly reported problems in the measurement of distribution coefficients using a shake-flask method such as mixing technique, speed and time, the temperature of experiment, type of buffer and its pH as well as n-octanol/buffer phase ratio. The concentration of compounds in the buffer is determined by HPLC directly from shake flasks or conventional 2-mL vials. The developed method was fully validated according to ICH guidelines. Furthermore, experimental data were successfully compared with lipophilicity and human intestinal absorption calculated by the use of four different theoretical approaches. The method shows potential for high-throughput measurements of a large number of compounds.

Miniaturized shake-flask HPLC method for determination of distribution coefficient of drugs used in inflammatory bowel diseases

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

A new method for determination of distribution coefficient of drugs azathioprine, 6-mercaptopurine and 6-thioguanine and nutrient folic acid used in the...

Miniaturized shake-flask HPLC method for determination of distribution coefficient of drugs used in inflammatory bowel diseases

Publié en ligne: 21 oct. 2019

Pages: 649 - 660

Accepté: 09 juin 2019

DOI: https://doi.org/10.2478/acph-2019-0046

Mots clés
distribution coefficient logarithm, shake-flask, HPLC, inflammatory bowel disease

© 2019 Edvin Brusač et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Miniaturized shake-flask HPLC method for determination of distribution coefficient of drugs used in inflammatory bowel diseases

Publié en ligne: 21 oct. 2019

Pages: 649 - 660

Accepté: 09 juin 2019

DOI: https://doi.org/10.2478/acph-2019-0046

Mots clésdistribution coefficient logarithm, shake-flask, HPLC, inflammatory bowel disease

© 2019 Edvin Brusač et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mots clés
distribution coefficient logarithm, shake-flask, HPLC, inflammatory bowel disease