adonifoline and senecionine

Pyrrolizidine alkaloids (PAs) are considered to be one of the most hepatotoxic groups of compounds of plant origin and are present in about 3% of the world's flowering plants. Most PAs represent a considerable health hazard to both livestock and humans through the consumption of plants and PA-contaminated products such as milk, honey, herbal teas, and medicines. This study determined the differences in the in vivo pharmacokinetic behavior of senecionine (SEN), adonifoline (ADO), and their main metabolites in rats after intravenous administration and oral administration by ultraperformance liquid chromatography/electrospray ionization mass spectrometry. Upon intravenous administration and oral administration of SEN and ADO, significant differences in pharmacokinetics were observed, with the SEN and ADO being absorbed fast with lower bioavailability and being quickly metabolized to PA N-oxides and hydroxylation products of PAs or their N-oxides. It could be seen that the plasma concentration ratio of senecionine N-oxide (SEN-NO) to SEN (C (SEN-NO)/C (SEN)) was significantly larger than that for adonifoline N-oxide (ADO-NO) and ADO (C (ADO-NO)/C (ADO)) (P < 0.001) for both dosing routes in rats. The high N-oxygenation activity and extensive toxicity of SEN, compared with ADO, in rats raised the question of whether or not the higher metabolic rate of SEN in rats in vivo was related to its potent toxicity. The toxicity of SEN-NO and ADO-NO needs to be evaluated further and compared in vitro/in vivo. This study was most helpful for interpreting the metabolism of metabolic bioactivation and detoxication, and toxicity differences among SEN, ADO and other PAs.

Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Injections, Intravenous; Lactones; Male; Pyrrolizidine Alkaloids; Rats; Rats, Sprague-Dawley; Senecio; Spectrometry, Mass, Electrospray Ionization

To develop an UPLC-MS method for the simultaneously quantitation of adonifoline and senecinine in Senecio herbs.. UPLC-Micro 2000 was used for quantification in SIR mode under ESI+. Monocrotaline was used as the internal standard. Chromatography was performed on a Shiseido Capcell Pak MG (2.0 mm x 50 mm, 3 microm) column at 30 degrees C using an gradient elution of acetonitrile-0.5% formic acid in water at the flow rate of 0.3 mL x min(-1). The injection volume was 2 microL.. Good linearity was obtained for quantitation of adonifoline over the range of 1.02-816.00 microg x L(-1) (r = 0.998 0). And recoveries at different concentration levels were between 95.73% and 103.0% with RSDs no more than 2.5%. For quantification of senecionine, the linear range was between 1.08-860.56 microg x L(-1) (r = 0.997 6). And recoveries at different concentration levels were between 95.67% and 101.5% with RSDs no more than 2.3%. Good reproducibility and precision were also achieved.. The new developed UPLC method is sensitive, accurate and reliable enough for the quantitation of adonifoline and senecionine in Senecio herbs thus can be used for the limit detection of pyrrolizidne alkaloids in S. scandens. It can also be used for the identification of fake drugs of S. scandens such as S. vulgaris. The developed method was served for the quality evaluation of Herba Senecionis Scandentis.

Topics: Chromatography, Liquid; Lactones; Mass Spectrometry; Pyrrolizidine Alkaloids; Senecio

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.

Topics: Animals; Calibration; Chemistry Techniques, Analytical; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Lactones; Liver; Male; Models, Chemical; Pyrrolizidine Alkaloids; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization