Investigation of the stability of aromatic hydrazones in plasma and related biological material
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
PubMed
18294799
DOI
10.1016/j.jpba.2008.01.011
PII: S0731-7085(08)00041-1
Knihovny.cz E-zdroje
- MeSH
- aldehydy krev chemie MeSH
- chelátory železa chemie MeSH
- fosfáty chemie MeSH
- hemofiltrace MeSH
- hydrazony krev chemie MeSH
- isoniazid analogy a deriváty krev chemie MeSH
- koncentrace vodíkových iontů MeSH
- králíci MeSH
- kultivační média chemie MeSH
- molekulární struktura MeSH
- poločas MeSH
- pufry MeSH
- pyridoxal analogy a deriváty krev chemie MeSH
- sérový albumin hovězí chemie MeSH
- skot MeSH
- stabilita léku MeSH
- teplota MeSH
- vysokoúčinná kapalinová chromatografie přístrojové vybavení metody MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- aldehydy MeSH
- chelátory železa MeSH
- fosfáty MeSH
- hydrazony MeSH
- isoniazid MeSH
- kultivační média MeSH
- pufry MeSH
- pyridoxal 2-chlorobenzoyl hydrazone MeSH Prohlížeč
- pyridoxal isonicotinoyl hydrazone MeSH Prohlížeč
- pyridoxal MeSH
- salicylaldehyde isonicotinoyl hydrazone MeSH Prohlížeč
- sérový albumin hovězí 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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