超高效液相串联质谱法测定大鼠西酞普兰及其代谢物的血药浓度

来源 :中国临床药理学杂志 | 被引量 : 0次 | 上传用户:nixijiunianzhi
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目的建立快速测定大鼠体内西酞普兰及其代谢物(N-氧化西酞普兰和N-去甲基西酞普兰)浓度的超高效液相串联质谱法。方法用乙酸乙酯萃取法处理血浆,色谱柱为ACQUITY UPLC BEH C18柱(50 mm×2.1 mm,1.7μm);流动相为乙腈-0.1%甲酸水,梯度洗脱,流速为0.4 m L·min-1;用正离子多离子反应监测(MRM)扫描,内标为曲马多。结果血浆中西酞普兰、N-去甲基西酞普兰和N-氧化西酞普兰的线性范围分别为0.1~10.0,0.1~10.0,0.01~2.00 ng·m L-1(r=0.999 1,0.999,0.999 6),定量下限分别为0.05,0.05,0.01ng·m L-1。其回收率分别在96.09%~105.33%。三者的日内、日间精密度均RSD<8.69%。结论该方法操作简便、快捷,灵敏度高,适于大鼠体内西酞普兰及其代谢物的药代动力学研究。 OBJECTIVE To establish a rapid ultra performance liquid chromatography-tandem mass spectrometry method for the rapid determination of citalopram and its metabolites (citalopram N-oxide and N-desmethylcitalopram) in rats. Methods The plasma was extracted with ethyl acetate. The column was ACQUITY UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm). The mobile phase consisted of acetonitrile - 0.1% formic acid water with gradient elution at a flow rate of 0.4 mL · min -1; positive ionized multiple ion reaction monitoring (MRM) scan, the internal standard is tramadol. Results The linear ranges of citalopram, n-desmethylcitalopram and citalopram in plasma were 0.1-10.0,0.1-10.0,0.01-2.00 ng · m L -1 (r = 0.999, 1.999 , 0.999 6). The lower limit of quantification was 0.05, 0.05 and 0.01 ng · m L-1, respectively. The recovery rates were 96.09% ~ 105.33%. The intra-day and inter-day precision RSD <8.69%. Conclusion The method is simple, rapid and sensitive. It is suitable for the pharmacokinetic study of citalopram and its metabolites in rats.
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