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Simultaneous determination of senecionine, adonifoline and their metabolites in rat serum by UPLC–ESIMS and its application in pharmacokinetic studies
- Source :
- Journal of Pharmaceutical and Biomedical Analysis. 50:1070-1074
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- A rapid, selective and sensitive ultra-performance liquid chromatography-electrospray ionization mass spectrometry (UPLC-ESIMS) method was firstly developed and validated for the simultaneous determination of two hepatotoxic pyrrolizidine alkaloids (HPAs), senecionine (SEN), adonifoline (ADO), and their N-oxides (SENNOX and ADONOX), the main metabolites in rat serum. The whole analysis was achieved within 4.5 min by gradient elution on an ACQUITY UPLC BEH C18 column (50 mm x 2.1 mm, i.d. 1.7 microm) following a solid phase extraction for serum samples. Good linearity was achieved using weighted (1/x2) least squares linear regression over a 1600-fold dynamic range for SEN and ADO (LLOQ was about 0.006 microg/ml) and 800-fold dynamic range for SENNOX and ADONOX (LLOQ was about 0.012 microg/ml). The R.S.D. of intra- and inter-day precision was below 4.91% and 11.15% respectively, while the R.E. of accuracy was within 4.52%, 6.81%, 2.69%, and 7.12% for SEN, SENNOX, ADO, and ADONOX, respectively. The developed method was successfully applied to the in vivo pharmacokinetic study in rats after intravenous administration of SEN and ADO.
- Subjects :
- Male
Spectrometry, Mass, Electrospray Ionization
Chemistry, Pharmaceutical
Metabolite
Clinical Biochemistry
Pharmaceutical Science
Mass spectrometry
High-performance liquid chromatography
Chemistry Techniques, Analytical
Analytical Chemistry
Rats, Sprague-Dawley
Lactones
chemistry.chemical_compound
Pharmacokinetics
Drug Discovery
Animals
Sample preparation
Solid phase extraction
Chromatography, High Pressure Liquid
Pyrrolizidine Alkaloids
Spectroscopy
Chromatography
Chemistry
Reproducibility of Results
Rats
Liver
Models, Chemical
Calibration
Pyrrolizidine
Senecionine
Subjects
Details
- ISSN :
- 07317085
- Volume :
- 50
- Database :
- OpenAIRE
- Journal :
- Journal of Pharmaceutical and Biomedical Analysis
- Accession number :
- edsair.doi.dedup.....ec6e34a5aedd9cdc48efb63c4483a08e