Overcoming challenges associated with the bioanalysis of an ester prodrug and its active acid metabolite
| Autor: | Hermes Licea Perez, Maria Busz, Dana Knecht |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Analyte
Bioanalysis Metabolite Clinical Biochemistry 030226 pharmacology & pharmacy 01 natural sciences Analytical Chemistry 03 medical and health sciences Hydrolysis chemistry.chemical_compound 0302 clinical medicine Ester prodrug Drug Stability Tandem Mass Spectrometry Sodium fluoride Organic chemistry Animals Prodrugs General Pharmacology Toxicology and Pharmaceutics Chromatography High Pressure Liquid Chromatography Chemistry 010401 analytical chemistry Temperature Esters General Medicine Prodrug 0104 chemical sciences Rats Medical Laboratory Technology Sodium Fluoride Dried Blood Spot Testing Ex vivo |
| Zdroj: | Bioanalysis. 9(20) |
| ISSN: | 1757-6199 |
| Popis: | Aim: Bioanalysis of ester prodrugs represents a great analytical challenge due to poor matrix stability in the presence of esterases. Materials & methods: An approach that includes pH control, temperature and the use of an inhibitor (sodium fluoride, NaF) was employed for complete stabilization of an ester prodrug and its corresponding acid metabolite. Stability information was used to design a methodology with negligible ex vivo hydrolysis of the ester to the corresponding acid analyte during all critical parts of bioanalysis. Results & conclusion: The assay was fully validated to regulatory expectations and employed to support a preclinical Good Laboratory Practice study in rats. Incurred sample reanalysis was also conducted and the percent difference between repeat and original results were within ±20%, thus confirming the repeatability of the assay. |
| Databáze: | OpenAIRE |
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