基于高效液相色谱-串联质谱技术检测贝母辛在小鼠体内的药动学与生物利用度  

Pharmacokinetics and bioavailability of peimisine in mice by high-performance liquid chromatography-tandem mass spectrometry

作　　者：涂安娜 江夏娟 陈玲 鲍曦 王贤亲 TU An-na;JIANG Xia-juan;CHEN Ling;BAO Xi;WANG Xian-qin(Department of Pharmacy,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang 325000,China;不详)

机构地区：[1]温州医科大学附属第一医院药学部,浙江温州325000 [2]温州医科大学分析测试中心,浙江温州325035 [3]温州医科大学司法鉴定中心,浙江温州325000

出　　处：《中国卫生检验杂志》2021年第18期2206-2209,2216,共5页Chinese Journal of Health Laboratory Technology

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UPLCMS/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。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 Clg column(2.1 mm×50 mm,1.7 m),column temperature was set at 30℃.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 0.0833h,0.5h,1h,2h,3h/4h,6h,8h 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-1000 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.

关 键 词：贝母辛 高效液相色谱-串联质谱法 药动学 生物利用度 

分 类 号：O657[理学—分析化学]