机构地区:[1]齐齐哈尔医学院药学院,黑龙江齐齐哈尔161006
出 处:《中国药房》2018年第20期2752-2757,共6页China Pharmacy
基 金:国家自然科学基金青年科学基金项目(No.81403173);黑龙江省教育科学"十三五"规划重点课题(No.GBB1318139);黑龙江省教育厅大学生创新创业训练计划项目(No.201611230027);黑龙江省留学回国人员择优资助项目(No.2017490);齐齐哈尔医学院院内科研基金项目(No.QY2016M-11)
摘 要:目的:建立测定大鼠血浆中莪术油多效应成分质量浓度的方法,并进行整合药动学研究。方法:16只大鼠单次灌胃莪术油提取液1.0 g/kg(按生药量计),分别于给药后0、0.17、0.5、1、2、2.5、3、4、6、8、10、12、24 h自眼眶取血300~400μL,采用气质联用法测定大鼠血浆中α-蒎烯、1,8-桉叶油素、龙脑、β-榄香烯、莪术醇、吉马酮、莪术二酮的质量浓度。色谱柱为DB-5毛细管柱,载气为氦气,进样口温度为270℃,柱温采用程序升温,流速为1.2 mL/min,分流比为20∶1,进样量为1μL;离子源为电喷雾离子源,以选择反应监测模式进行正离子扫描,扫描范围为m/z 20~500。采用DAS 2.0软件计算上述各效应成分的药动学参数,并以其AUC0-∞在AUC0-∞总和中所占的比例自定义权重系数,估算莪术油多效应成分在大鼠体内的整合药动学参数。结果:α-蒎烯、1,8-桉叶油素、龙脑、β-榄香烯、莪术醇、吉马酮、莪术二酮血药浓度的线性范围分别为2.71~173.54、7.76~496.88、3.37~215.72、21.68~1 387.50、40.21~2 573.44、24.84~3 179.69、47.78~3 057.81 ng/mL(r>0.99),定量下限分别为2.71、7.76、3.37、21.68、40.21、24.84、47.78 ng/mL,精密度、准确度、基质效应等均符合生物样品定量分析的相关要求。α-蒎烯、1,8-桉叶油素、龙脑、β-榄香烯、莪术醇、吉马酮、莪术二酮的cmax分别为(34.72±9.97)、(99.86±5.54)、(16.10±3.37)、(248.98±86.19)、(673.75±104.15)、(2 353.64±637.83)、(2 420.04±708.51)ng/mL;tmax分别为(2.33±0.29)、(0.67±0.29)、(1.33±0.58)、(1.83±0.76)、(0.83±0.29)、(0.89±0.18)、(1.17±0.76)h;t1/2分别为(8.64±1.46)、(8.98±1.63)、(12.43±2.88)、(19.86±4.05)、(15.63±5.50)、(14.17±4.13)、(7.14±0.67)h;AUC0-t分别为(189.78±89.10)、(454.74±82.43)、(100.55±8.27)、(1 067.37±216.55)、(3 154.16±405.94)、(16 501.24±663.88)、(12 524.92±3 222.10)ng·h/mL;AUC0-∞分别为(229.57±93.50)、(524.32±81.67)、(14OBJECTIVE:To develop the determination method for plasma concentration of effective components in essential oil from Curcuma phaeocaulis,and to study its integrated pharmacokinetics.METHODS:Sixteen rats were given the extract of essential oil from C.phaeocaulis 1.0 g/kg(by crude drug)intragastrically;blood samples 300-400μL from orbit were collected 0,0.17,0.5,1,2,2.5,3,4,6,8,10,12,24 h after medication.The plasma concentration ofα-pinene,1,8-cineole,borneol,β-elemene,curcumol,germacrone and curdione in rats were determined by GC-MS.The determination was performed on DB-5 capillary column,using helium as carrier gas,at the flow rate of 1.2 mL/min.The injector temperature was 270℃,by temperature programming,and split ratio was 20∶1.The sample size was 1μL.The ion source was electrospray ion source.The selective reaction monitoring mode was used for the positive ion scanning in the range of m/z 20-500.Pharmacokinetic parameters of above effective components were calculated by using DAS 2.0 software.The weight coefficients were customized according to the proportion of AUC0-∞in the sum of AUC0-∞.The integrated pharmacokinetic parameters of multiple effective components in essential oil from C.phaeocaulis were calculated.RESULTS:The linear range ofα-pinene,1,8-cineole,borneol,β-elemene,curcumol,germacrone,and curdione were 2.71-173.54,7.76-496.88,3.37-215.72,21.68-1 387.50,40.21-2 573.44,24.84-3 179.69,47.78-3 057.81 ng/mL,respectively(r>0.99).The lower limits of quantitation were 2.71,7.76,3.37,21.68,40.21,24.84,47.78 ng/mL,respectively.The precision,accuracy and matrix effects were in line with related requirements of quantitative analysis of biological samples.The pharmacokinetic parameters ofα-pinene,1,8-cineole,borneol,β-elemene,curcumol,germacrone,and curdione were as follows that cmax were(34.72±9.97),(99.86±5.54),(16.10±3.37),(248.98±86.19),(673.75±104.15),(2 353.64±637.83),(2 420.04±708.51)ng/mL;tmax were(2.33±0.29),(0.67±0.29),(1.33±0.58),(1.83±0.76),(0.83±0.29),(0.89±0.18),(1.1
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