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Enantioseparation and Determination of Penconazole in Rat Plasma by Chiral LC-MS/MS: Application to a Stereoselective Toxicokinetic Study

机译:手性LC-MS / MS对大鼠血浆中潘康唑的鉴定和测定方法:应用于立体选择性毒性研究

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摘要

In this study, a specific and sensitive method of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed for the determination of penconazole enantiomers in rat plasma. The enantioseparation was achieved on a Chiralpak IC column by using acetonitrile/water (80:20, / ) as the mobile phase. Penconazole enantiomers and internal standard -lansoprazole (IS) were detected in multiple reaction monitoring (MRM) mode with positive electrospray ionization source. The method was validated over the concentration range of 2.5–250.0 ng mL for penconazole enantiomers. Good linearity was obtained for both enantiomers with correlation coefficients ( ) greater than 0.995. The relative error was well within the admissible range of −1.1–3.2%, and relative standard deviation was less than 6.0%. After validation, the established method was successfully applied to a stereoselective toxicokinetic study in female and male rats after oral administration of 50 mg kg racemic penconazole. This is the first experiment regarding the stereospecific toxicokinetic study of penconazole and the bioanalytical approach for its quantitation in vivo.
机译:在该研究中,开发了一种与串联质谱(LC-MS / MS)偶联的液相色谱法的特定和敏感方法用于测定大鼠等离子体中的潘尼尼唑对映异构体。通过使用乙腈/水(80:20,/)作为流动阶段,在Chiralpak IC柱上进行酶分子。在具有正电喷雾电离源的多反应监测(MRM)模式下检测潘康唑对映异构体和内标--Lanso1唑(IS)。将该方法验证在2.5-250.0ng ml的浓度范围内,对于潘康唑对映异构体。对于具有大于0.995的相关系数()的对映体获得良好的线性度。相对误差良好在允许的范围内-1.1-3.2%,相对标准偏差小于6.0%。验证后,成熟的方法已成功应用于口服施用50mg kg外消旋潘尼诺唑后的女性和雄性大鼠的立体选择性毒性研究。这是关于潘康唑立体毒性研究的第一个实验和体内定量的生物分析方法。

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