Monocrotaline (MCT) is a pyrrolizidine alkaloid which can induce hepatic sinusoidal damage, pulmonary hypertension, renal toxicity and heart disease. Monocrotaline N-oxide (MNO), the primary metabolite of MCT, is less toxic, however it can convert back into MCT to exhibit its toxicity. In present study, a rapid and sensitivity LC-MS/MS method for simultaneous determination of MCT and MNO in rat plasma was developed and validated. The method was linearity over concentration range of 1 to 2000 ng/mL with correlation coefficients (r) > 0.997 for each analyte. The results of selectivity, matrix effect, accuracy and precision, recovery were all within the acceptance criteria. The validated method has been successfully applied to study pharmacokinetic behaviors and bioavailability of MCT in rats. The MCT was rapid absorbed (Tmax: 0.400 ± 0.149 h) after oral administration of MCT, and the absolute bioavailability of MCT was 78.2%.
Monocrotaline (purity > 99%), monocrotaline N-oxide (purity > 98%) and erucifoline (ERU,
purity > 98%) were purchased from Fluorochem Ltd. (Hadfield, UK), Chengdu Biopurify
Phytochemicals Ltd. (Chengdu, China)
