【摘要】 目的建立人血浆中环维黄杨星D的测定方法,评价环维黄杨星D分散片与普通片剂在中国健康成年男性志愿者中的生物等效性。方法以左羟丙哌嗪为内标,血浆样品经氯仿萃取,Hyperity C18柱(150 mm×2.1 mm,5μm)分离后,采用高效液相色谱-串联质谱法检测。18名健康男性志愿者采用双周期随机交叉试验设计,分别单剂量口服环维黄杨星D分散片与普通片剂2 mg。结果环维黄杨星D与内标分离度好,内源性杂质不干扰测定,质量浓度在10～320 pg/mL(r=0.996 9)与峰面积比的线性关系良好,定量下限为10 pg/mL,萃取回收率为82.66%～89.58%(n=5),日内RSD为4.17%～9.96%(n=5),日间RSD为5.21%～10.31%(n=15)。单次服用2 mg环维黄杨星D分散片和普通片剂后的0～144 h药时曲线下面积(AUC0～144)分别为(5679.83±1548.21)pg.h/mL和(5 243.65±1 317.39)pg.h/mL,0～∞药时曲线下面积(AUC0～∞)分别为(7 464.21±2 128.08)pg.h/mL和(7 021.43±2 076.12)pg.h/mL,峰浓度(Cmax)分别为(202.81±43.30)pg/mL和(222.10±50.90)pg/mL,达峰时间(tmax)分别为(5.76±1.93)h和(5.22±1.03)h,半衰期(t1/2)分别为(54.67±12.43)h和(50.66±13.63)h。与普通片剂相比,环维黄杨星D分散片的相对生物利用度为(100.5±10.1)%。结论该方法准确度高、灵敏度好,可用于环维黄杨星D人体内过程研究。两种制剂为生物等效制剂。更多还原

【Abstract】 Objective To establish a HPLC-MS-MS method for the determination of cyclovirobuxine-D in plasma and to compare the relative bioavailability of Cyclovirobuxine-D Dispersible Tablets and common tablets for evaluating the bioequivalence in Chinese healthy male volunteers.Methods With levodropropizine as the internal standard,the plasma sample was extracted by chloroform and separated by the Hyperity C18 column(150 mm×2.1 mm,5 μm).HPLC-MS-MS was carried out with the mobile phase consisting.A cross over bioavailability trial was designed and 18 Chinese healthy male volunteers and each group was orally given Cyclovirobuxine-D Dispersible Tablets or common tablets 2 mg.The pharmacokinetic parameters and relative bioavailability were calculated to evaluate the bioequivalence of the two preparations.Results The calibration curve was linear within 10-320 pg/mL-1(r=0.996 9).The extraction recovery rate of cyclovirobuxine-D was 82.66%-89.58%(n=5),and the intra-day and inter-day RSD 4.17%-9.96%(n=5),and 5.21%-10.31%(n=15),respectively.The AUC0～144 of the two tablets was(5 679.83±1 548.21)(pg·h)/mL and(5 243.65±1 317.39)(pg·h)/mL,AUC0～∞(7 464.21±2 128.08)(pg·h)/mL and(7 021.43±2 076.12)(pg·h)/mL,Cmax(202.81±43.30)pg/mL and(222.10±50.9) pg/mL,Tmax(5.76±1.93)h and(5.22±1.03)h,and T1/2(54.67±12.43)h and(50.66±13.63)h.The relative bioavailability of dispersible tablets to reference tablets was(100.5±10.1)%.Conclusion The established HPLC-MS-MS method is accurate and sensible,which can be used to study the pharmacokinetics of cyclovirobuxine-D.There is no significant difference between the two tablets,and they are bioequivalent.更多还原