Abstract
Background and Aims The present study aimed to develop a simple and sensitive method for quantitative determination of monocrotaline (MCT) in mouse blood employing ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI/MS/MS) using rhynchophylline as an internal standard. Methods Proteins present in the blood samples were precipitated using acetonitrile. MCT was separated using a 1.7-μm ethylene bridged hybrid (BEH) C18 column (2.1 mm × 50 mm) with a gradient elution program and a constant flow rate of 0.4 mL/min. The LC mobile phase consisted of 10 mmol/L ammonium acetate (containing 0.1% formic acid) and acetonitrile. The total elution time was 4.0 min. The analytes were detected on a UPLC-ESI mass spectrometer in multiple reaction monitoring (MRM) mode and quantified. Results The new method for the determination of MCT has a satisfactory linear detection range of 1-2000 ng/mL and excellent linearity (r = 0.9971). The lower limit of quantification (LLOQ) of MCT is 1.0 ng/mL. Intra- and interassay precisions of MCT were ≤13% with an accuracy from 96.2% to 106.6%. The average recovery of the new method was >75.0%, and matrix effects were between 89.0% and 94.3%. Based on the pharmacokinetics data, the bioavailability of MCT in mice was 88.3% after oral administration. Conclusions The results suggest that the newly standardized method for quantitative determination of MCT in whole blood is fast, reliable, specific, sensitive, and suitable for pharmacokinetic studies of MCT after intravenous or intragastric administration.
Highlights
Monocrotaline, a pyrrolizidine alkaloid (PA) isolated from Crotalaria species, induces toxicity in many tissues and causes extreme hepatic necrosis, pulmonary hypertension, and severe kidney damage [1]
It is well known that pharmacokinetic studies play a pivotal role in drug development, as they assist in predicting a variety of efficacy- and toxicity-related events
There was increased sensitivity and selectivity when UPLC-MS/MS was used for the quantitative determination of MCT utilizing 20 μL mouse blood as compared to the traditional high-performance liquid chromatography (HPLC)
Summary
Monocrotaline (crotaline, MCT), a pyrrolizidine alkaloid (PA) isolated from Crotalaria species, induces toxicity in many tissues and causes extreme hepatic necrosis, pulmonary hypertension, and severe kidney damage [1]. To better understand how the toxicity and the pharmacological activity of MCT in vivo change with the blood concentration, a rapid, simple, and effective analytical method is necessary. The present study aimed to develop a simple and sensitive method for quantitative determination of monocrotaline (MCT) in mouse blood employing ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI/MS/MS) using rhynchophylline as an internal standard. The new method for the determination of MCT has a satisfactory linear detection range of 1-2000 ng/mL and excellent linearity (r = 0.9971). The results suggest that the newly standardized method for quantitative determination of MCT in whole blood is fast, reliable, specific, sensitive, and suitable for pharmacokinetic studies of MCT after intravenous or intragastric administration
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