摘要
目的:建立测定大鼠血浆中芥子碱硫氰酸盐、槲皮素和山柰酚含量的方法,并研究大鼠体内芪苈强心胶囊的药动学。方法:采用高效液相色谱-串联质谱(HPLC-MS/MS)法。色谱柱为ZOBRAX XDB-C18,流动相为0.1%甲酸水溶液-含0.1%甲酸的乙腈溶液(梯度洗脱),流速为0.45 mL/min,进样量为10μL,定量离子为芥子碱硫氰酸盐质荷比(m/z)310.2→251.2,槲皮素m/z301.1→150.7,山柰酚m/z 286.2→242.0,内标氯霉素m/z 320.9→151.9。6只大鼠灌胃给予芪苈强心胶囊1.3 g/kg后0.083、0.167、0.333、0.667、1、1.5、2、3、4、6、8、12、24 h经目内眦静脉丛取血,并测定芥子碱硫氰酸盐、槲皮素和山柰酚的血药浓度。采用DAS3.0软件拟合计算各药动学参数。结果:芥子碱硫氰酸盐、槲皮素和山柰酚的检测质量浓度线性范围分别为0.05~100、0.1~200、0.1~200 ng/mL(r=0.999 4、0.999 7、0.999 9),精密度试验及基质效应RSD均≤11.55%(n=6),稳定性试验RE≤14.69%(n=3)。芥子碱硫氰酸盐、榭皮素和山柰酚在大鼠体内的cmax分别为(1.35±0.62)、(3.23±1.26)、(5.27±1.66)ng/mL,tmax分别为(1.50±0.00)、(0.67±0.00)、(0.67±0.00)h,t1/2分别为(3.98±0.99)、(3.33±0.41)、(4.54±0.85)h,CL分别为(3 683.82±987.96)、(2 852.33±695.88)和(1 611.85±129.59)mL/(h·kg),AUC0-24h分别为(3.98±1.21)、(10.96±3.42)和(13.59±5.35)h·ng/mL。结论:该检测方法灵敏度高、专属性强、重复性好,适用于芪苈强心胶囊中芥子碱硫氰酸盐、槲皮素和山柰酚在大鼠体内的药动学研究。
OBJECTIVE:To establish a method for the content determination of sinapine thiocyanate,quercetin and kaempferol in rat plasma,and to study pharmacokinetics of Qili qiangxin capsule in rats in vivo.METHODS:HPLC-MS/MS method was adopted.The determination was performed on ZOBRAX XDB-C18 column with mobile phase consisted of 0.1% formic acid solution and acetonitrile containing 0.1% formic acid(gradient elution)at the flow rate of 0.45 mL/min.The sample size was 10μL.Quantitative ions were sinapine thiocyanate with m/z 310.2→251.2,quercetin with m/z 301.1→150.7,kaempferol with m/z286.2→242.0,internal standard chloramphenicol with m/z 320.9→151.9.0.083,0.167,0.333,0.667,1,1.5,2,3.,4,6,8,12,24 h after intragastric administration of Qili qiangxin capsule 1.3 g/kg,blood samples were collected via intraocular canthal venous plexus of 6 rats.The blood concentrations of sinapine thiocyanate,quercetin and kaempferol were determined.The pharmacokinetic parameters were calculated and fitted by using DAS 3.0 software.RESULTS:The linear range of sinapine thiocyanate,quercetin and kaempferol 0.05-100,0.1-200,0.1-200 ng/mL(r=0.999 4,0.999 7,0.999 9);RSDs of precision test and matrix effect were all less than or equal to 11.55%(n=6),RE of stability test is less than or equal to 14.69%(n=3).The pharmacokinetic parameter of sinapine thiocyanate,quercetin and kaempferol included that cmax were(1.35 ± 0.62),(3.23 ± 1.26),(5.27 ± 1.66)ng/mL;tmax were(1.50±0.00),(0.67±0.00),(0.67±0.00)h;t1/2 were(3.98±0.99),(3.33±0.41),(4.54±0.85)h;CL were(3 683.82±987.96),(2 852.33 ±695.88),(1 611.85 ±129.59)mL/(h·kg);AUC0-24、were(3.98± 1.21),(10.96±3.42),(13.59±5.35)h·ng/mL.CONCLUSIONS:Established method is highly sensitive,specific and reproducible,and suitable for the pharmacokinetic study of sinapine thiocyanate,quercetin and kaempferol in rat.
作者
张瑜
张富赓
张少强
朱明丹
肖学凤
杜武勋
ZHANG Yu;ZHANG Fugeng;ZHANG Shaoqiang;ZHU Mingdan;XIAO Xuefeng;DU Wuxun(College of Postgraduate,Tianjin University of TCM,Tianjin 301617, China;Dept. of Pharmacy,Tianjin Huanhu Hospital,Tianjin 300350,China;Dept. of Cardiovascular Medicine,the Second Affiliated Hospital of Tianjin University of TCM,Tianjin 300150,China;College of TCM,Tianjin University of TCM,Tianjin 301617,China)
出处
《中国药房》
CAS
北大核心
2019年第15期2042-2046,共5页
China Pharmacy
基金
国家自然科学基金资助项目(No.81774227)
天津市自然科学基金资助项目(No.17JCZDJC34600)
天津市中医中西医结合科研课题(No.2015050)
