【摘要】 目的建立高效液相色谱-串联质谱法（UPLC-MS/MS）检测小鼠血液中贝母辛,并研究贝母辛在小鼠体内的不同给药方式的药代动力学;静脉（1 mg/kg）、口服（2 mg/kg、4 mg/kg、8 mg/kg）给药,并计算绝对生物利用度。方法采用UPLC BEH C₁₈色谱柱（2.1 mm×50 mm,1.7μm）,柱温设为30℃。流动相为乙腈和0.1%甲酸,采用梯度洗脱,流速设为0.4 ml/min,洗脱时间4 min。采用电喷雾离子源（ESI）,正离子模式,多重反应监测（MRM）模式扫描检测。ICR小鼠在静脉或口服贝母辛后的0.083 3 h、0.5 h、1 h、2 h、3 h、4 h、6 h、8 h、12 h尾静脉取血。建立UPLC-MS/MS法测定各组血药浓度,采用DAS 2.0软件进行数据分析,使用非房室模式进行拟合药动学参数。结果贝母辛在1 ng/ml～1 000 ng/ml浓度内呈良好的线性关系（r>0.998）;日内精密度<14%,日间精密度<15%,准确度为92.3%～111.3%。在小鼠体内半衰期比较短,生物利用度为19.2%。结论UPLC-MS/MS法适用于贝母辛在小鼠体内的药动学研究,贝母辛在小鼠体内代谢较快,口服生物利用度较小。更多还原

【Abstract】 Objective To establish a high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）method to detect peimisine in the blood of mice,and study the pharmacokinetics of peimisine in mice by different administration methods.One group was administered intravenously （1 mg/kg） and the other groups taken orally （2 mg/kg,4 mg/kg,8 mg/kg）,and the absolute bioavailability was calculated.Methods Using BEH C₁₈column （2.1 mm×50 mm,1.7 m）,column temperature was set at 30°C.The mobile phase was acetonitrile and 0.1%formic acid,and the gradient elution procedure was used.The flow rate was set at 0.4 ml/min and the elution time was 4 min.ESI positive ion mode and MRM mode were used.Blood samples were taken from the caudal vein of ICR mice at 0.083 3 h,0.5 h,1 h,2 h,3 h,4 h,6 h,8 h and 12 h after intravenous or oral administration of peimisine.UPLC-MS/MS was used for the determination of blood concentrations.DAS 2.0 software was used to analyze the data and the pharmacokinetic parameters were fitted by non-atrioventricular model.Results Good linearity was observed in the range of 1 ng/ml-1 000 ng/ml （r>0.998）,with intra-day precision RSD<14%,intra-day precision RSD<15%,and accuracy range of 92.3%-111.3%.In mice,the half-life is relatively short,and the bioavailability is 19.2%.Conclusion UPLC-MS/MS method is suitable for the pharmacokinetic study of peimisine in mice.The metabolism of peimisine in mice is faster and the oral bioavailability of peimisine is lower.更多还原