JA0021 A quantitative determination of fluorochloridone in rat plasma by UPLC-MS/MS method: application to a pharmacokinetic study
来源:Biomedical Chromatography
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作者:Shihong Liu
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发布时间: 1711天前
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1802 次浏览
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: A precise, high-throughput and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method has been developed for the determination of fluorochloridone (FLC) in rat plasma. The extraction of analytes from plasma samples was carried out by protein precipitation procedure using acetonitrile prior to UPLC-MS/MS analysis. Verapamil was proved as a proper internal standard (IS) among many candidates. The chromatographic separation based on UPLC was well optimized. Multiple reaction monitoring in positive electrospray ionization was used with the optimized MS transitions at: m/z 312.0 → 292.0 for FLC and m/z 456.4 →165.2 for IS. This method was well validated with good linear response (r 2 > 0.998) observed over the investigated range of 3–3000 ng/mL and with satisfactory stability. This method was also characterized with adequate intra- and inter-day precision and accuracy (within 12%) in the quality control samples, and with high selectivity and less matrix effect observed. Total running time was only 1.5 min. This method has been successfully applied to a pilot FLC pharmacokinetic study after oral administration.
1 Introduction
With the growing use of herbicides, human
health is faced with chronic harmful effects of herbicide residues in
vegetables and other foods, such as hormone imbalance (Rieke et al., 2014),
nervous system damage (Wu et al., 2012) and fertility disorder (Lotter, 2015).
Fluorochloridone (FLC) is a herbicide widely used for preemergence control of
broad-leaved weeds. It is a mixture of cisand trans- diastereoisomer pairs. The
European Food Safety Authority has reported that FLC is considered a potential
endocrine disruptor and the no observed adverse effect level is 20 mg/kg
b.w./day, with the lowest observed adverse effect level 25 mg/k.g. bw/day
(European Food Safety Authority, 2010). An assay of 90 days toxicity of FLC by
repeated oral administration in rats showed that liver and hematopoietic
systems were the main target organs except for lesions of testis and epididymis
depending on the dose of FLC (Zhang et al., 2015).....
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