Investigation of the stability of aromatic hydrazones in plasma and related biological material
Language English Country Great Britain, England Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
18294799
DOI
10.1016/j.jpba.2008.01.011
PII: S0731-7085(08)00041-1
Knihovny.cz E-resources
- MeSH
- Aldehydes blood chemistry MeSH
- Iron Chelating Agents chemistry MeSH
- Phosphates chemistry MeSH
- Hemofiltration MeSH
- Hydrazones blood chemistry MeSH
- Isoniazid analogs & derivatives blood chemistry MeSH
- Hydrogen-Ion Concentration MeSH
- Rabbits MeSH
- Culture Media chemistry MeSH
- Molecular Structure MeSH
- Half-Life MeSH
- Buffers MeSH
- Pyridoxal analogs & derivatives blood chemistry MeSH
- Serum Albumin, Bovine chemistry MeSH
- Cattle MeSH
- Drug Stability MeSH
- Temperature MeSH
- Chromatography, High Pressure Liquid instrumentation methods MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Cattle MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Aldehydes MeSH
- Iron Chelating Agents MeSH
- Phosphates MeSH
- Hydrazones MeSH
- Isoniazid MeSH
- Culture Media MeSH
- Buffers MeSH
- pyridoxal 2-chlorobenzoyl hydrazone MeSH Browser
- pyridoxal isonicotinoyl hydrazone MeSH Browser
- Pyridoxal MeSH
- salicylaldehyde isonicotinoyl hydrazone MeSH Browser
- Serum Albumin, Bovine MeSH
Novel aromatic hydrazones derived from pyridoxal isonicotinoyl hydrazone (PIH) are interesting compounds from the viewpoint of their pharmacodynamic activity. However, they were recently shown to suffer from relatively short biological half-lives. The purpose of the present study was to investigate the stability of novel aroylhydrazones in plasma and related biological media in order to reveal its potential involvement in the pharmacokinetics of these drugs. Three different aroylhydrazones (pyridoxal isonicotinoyl hydrazone - PIH, salicylaldehyde isonicotinoyl hydrazone - SIH and pyridoxal 2-chlorobenzoyl hydrazone - o-108) were incubated in plasma from different species, plasma ultrafiltrate, bovine serum albumin, RPMI cell medium and phosphate buffer saline (PBS) at 37 degrees C. Stability of these compounds was determined using precise, selective and validated HPLC methods. Although the aroylhydrazones were relatively stable in PBS, they underwent rapid degradation in plasma. Plasma proteins as well as low molecular weight components were involved in this matter. Furthermore, the products of hydrazone bond splitting revealed in this study were also found in the chromatograms from pharmacokinetic experiments. In the light of short biological half-lives determined in vivo, these in vitro findings strongly suggest that hydrolysis of investigated aromatic hydrazones in plasma could have a significant impact on their pharmacokinetics. Furthermore, these results also suggest that plasma stability of other novel drug candidates containing the hydrazone bond deserves to be considered.
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