Simultaneous determination of senecionine, adonifoline and their metabolites in rat serum by UPLC-ESIMS and its application in pharmacokinetic studies.
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.
Xiong
Aizhen
A
Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
Li
Yan
Y
Yang
Li
L
Gao
Jiangguo
J
He
Yuqi
Y
Wang
Changhong
C
Wang
Zhengtao
Z
D000818:Animals; D002138:Calibration; D002623:Chemistry Techniques, Analytical; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007783:Lactones / Q000097:blood* / Q000378:metabolism*; D008099:Liver / Q000187:drug effects; D008297:Male; D008956:Models, Chemical; D011763:Pyrrolizidine Alkaloids / Q000097:blood* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D007783:Lactones; D011763:Pyrrolizidine Alkaloids; C546218:adonifoline; C009237:senecionine