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目的用液相色谱-质谱联用仪(high performance liquid chromatography/mass spectrometry,HPLC/MS)建立氯硝柳胺在小鼠血浆、肌肉和皮肤中的定量分析方法,并用于药代动力学,为氯硝柳胺抗尾蚴侵袭新剂型的研究及药物残留测定方法的建立提供实验数据支持。方法采用丙酮提取生物样品中的氯硝柳胺,以对硝基酚为内标,以两者的[M-H]-准分子离子峰m/z 324.9788和138.0186为单离子监测(SIM)产物离子进行定量分析,测定氯硝柳胺在血浆、肌肉和皮肤中的药物含量和药时曲线,计算药峰浓度(C_(max))、生物半衰期(T_(1/2))及药时曲线下面积(AUC)。结果小鼠口服200mg/kg氯硝柳胺后在血浆、肌肉和皮肤C_(max)分别为(2251.22±31.38)、(250.52±41.99)和(3663.01±1279.52)ng/ml,T_(1/2)分别为(11.07±0.88)、(45.57±0.66)和(14.67±0.31)h,AUC分别为(23237.±544)、(8458±581)和(79 093±1 060)ng/(h·ml)。结论氯硝柳胺在小鼠体内的含量测定结果表明,其在皮肤中C_(max)及AUC均为最高,说明其易于在皮肤中分布。该性质有利于抗血吸虫尾蚴的侵袭。
Objective To establish a method for the quantitative analysis of niclosamide in plasma, muscle and skin of mice by using high performance liquid chromatography / mass spectrometry (HPLC / MS) and to study the pharmacokinetics of Niclosamide anti-cercariae invasion of new formulations and determination of drug residues established experimental data to provide support. Methods Niclosamide in biological samples was extracted with acetone and p - nitrophenol was used as an internal standard. The [MH] - excimer ion peaks m / z 324.9788 and 138.0186 of both were used as single ion monitoring (SIM) product ions Quantitative analysis of niclosamide in the plasma, muscle and skin of the drug content and drug-time curve, calculated peak drug concentration (C max), biological half-life (T 1/2) and the area under the curve (AUC). Results After oral administration of 200mg / kg niclosamide, the maximal C max values in plasma, muscle and skin of mice were (2251.22 ± 31.38), (250.52 ± 41.99) and (3663.01 ± 1279.52) ng / ml, respectively ) Were (11.07 ± 0.88), (45.57 ± 0.66) and (14.67 ± 0.31) h, respectively. The AUC were 23237. ± 544, 8458 ± 581 and 79 093 ± 1060 ng / ml). Conclusion The results of the determination of niclosamide in mice showed that C_ (max) and AUC were the highest in the skin, indicating that it is easy to distribute in the skin. This property is conducive to the invasion of anti-schistosome cercariae.