ABSTRACT
Liquid chromatography-ion trap mass spectrometry (LC/ITMS) was employed for a metabolic kinetics study of tert-butylhydroquinone (TBHQ) and its metabolites in rat serum after oral administration. The mean serum concentration-time data of TBHQ and its four metabolites (M1-M4) in both male and female rats after oral administration of TBHQ at dosages of 7, 350 and 700 mg/kg were all best-fitted by a two-compartment model with first-order absorption. TBHQ was rapidly absorbed, distributed and metabolized. The metabolites were also distributed rapidly except M2, but eliminated more slowly than TBHQ. At the doses of 350 and 700 mg/kg, the total concentrations of TBHQ and its metabolites in serum were much higher for male than female rats during the metabolic process (P < 0.01). In addition, the serum concentrations of M1, M3 and M4 were all much higher for males than for females (P < 0.01) during the metabolic process, while no significant differences between male and female rats were found (P > 0.05) for TBHQ and M2, at the doses of 350 and 700 mg/kg. The exploratory assessment of dose proportionality for TBHQ and its metabolites by the power model indicated that the TBHQ exposure increased in a more-than-dose-proportional manner, but the exposures of the metabolites M1-M4 increased in a less-than-dose-proportional manner, across the dose of 7-700 mg/kg.
Subject(s)
Hydroquinones/chemistry , Hydroquinones/metabolism , Administration, Oral , Animals , Chromatography, Liquid , Female , Hydroquinones/administration & dosage , Kinetics , Male , Mass Spectrometry , Molecular Structure , RatsABSTRACT
In this article, human basic fibroblast growth factor (bFGF) loaded PCL-PEG-PCL (PCEC) nanoparticles were prepared by modified W1/O/W2 double emulsion solvent evaporation method. The bFGF encapsulated in PCEC nanoparticles could be released in sustained release behavior in vitro. After subcutaneous single-dose injection of bFGF loaded PCEC nanoparticles at 20 microg of bFGF per dose in mice, the anti-bFGF special autoantibody IgG continued to grow until 8 weeks after the immunization and was still kept at high level at week 11. At the same time, HK293 cell viability assay in vitro indicated that the cytotoxicity of blank PCEC nanoparticles was low but dose dependent. For some success in controlling tumor growth had been met by neutralizing bFGF reported previously, the bFGF loaded PCEC nanoparticles prepared in this paper might have potential application as anti-tumor vaccine.
Subject(s)
Fibroblast Growth Factor 2/administration & dosage , Nanoparticles , Polyesters/administration & dosage , Polyethylene Glycols/administration & dosage , Animals , Antibody Formation , Female , Fibroblast Growth Factor 2/immunology , Humans , Mice , Mice, Inbred BALB C , Microscopy, Electron, ScanningABSTRACT
A new method applying sensitive and selective liquid chromatography coupled with mass spectrometry (LC/MS/MS) for analyzing tertiary-butylhydroquinone (TBHQ) and its metabolites in rat serum was validated. Using an extracted ion chromatogram (EIC) of m/z 149, free TBHQ was observed in rat serum after dosing TBHQ at 350 mg/kg to male and female Sprague-Dawley (SD) rats. Four major metabolites of TBHQ were identified-a TBHQ-sulfate, two TBHQ-sulfate-derived substances and a TBHQ-glucuronide through MS(n) spectra. Besides its simplicity, the sample treatment allows one to obtain a very good recovery of analysts, namely around 95%. This result suggests that the method described here is useful for the analysis of TBHQ and its metabolites in rat serum. Moreover, the metabolism of TBHQ was investigated using the method. After oral administration, TBHQ appear to be more completely absorbed and bio-transformed by males than females, which may result in higher acute oral toxicity of TBHQ for males than females.
