[关键词]
[摘要]
目的 探讨丹酚酸B单体在正常大鼠和高脂血症大鼠体内的药动学特征.方法 复制大鼠高脂血症动物模型,建立丹酚酸B微透析样品的液质联用检测方法,研究丹酚酸B低、中、高剂量(25、50、100 mg/kg)ig给药的正常和高脂血症大鼠的药动学特征.采用微透析技术定时采样,微透析样品经体内回收率校正后液质联用检测,以采样时间中点对血药浓度建立药-时曲线,采用非房室模型拟合获得药动学参数.结果 正常大鼠丹酚酸B低、中、高剂量(25、50、100 mg/kg)主要药动学参数,达峰浓度(Cmax)分别为(38.551±6.692)、(95.550±12.544)、(204.251±20.342)ng/mL,达峰时间(tmax)分别为(1.125±0.000)、(1.375±0.125)、(1.125±0.125)h,药-时曲线下面积(AUC0~t)分别为(65.995±12.367)、(178.806±33.592)、(422.836±72.344)h·ng/mL,平均滞留时间(MRT)分别为(2.002±0.061)、(1.911±0.042)、(1.955±0.053)h;高脂血症大鼠丹酚酸B低、中、高剂量(25、50、100 mg/kg)主要药动学参数,Cmax分别为(49.265±7.317)、(113.986±15.294)、(246.454±30.476)ng/mL,tmax分别为(1.125±0.000)、(1.125±0.125)、(1.375±0.125)h,AUC0~t分别为(96.013±15.384)、(207.192±32.676)、(486.843±89.276)h·ng/mL,MRT分别为(2.161±0.049)、(2.089±0.033)、(2.097±0.035)h.结论 结果表明液质联用检测方法灵敏度高、专属性强,能够满足分析要求.高脂血症各剂量组丹酚酸B Cmax、AUC0~t 均高于正常组,平均滞留时间长于正常组,有利于体内长时间滞留来发挥疗效,但差异无统计学意义.
[Key word]
[Abstract]
Objective To study the pharmacokinetics of salvianolic acid B (Sal B) monomer in normal and hyperlipidemic rats. Methods The hyperlipidemic rat model was replicated successfully by using high fat diet. The detection method for microdialysis samples was established by using LC-MS. The pharmacokinetic study on Sal B in normal and hyperlipidemic rats was carried out after ig administration with low-, medium-, and high-dose (25, 50, and 100 mg/kg) Sal B using microdialysis sampling technology. The microdialysis samples were corrected with in vivo recoveries and followed by LC-MS detection. The plasma drug concentration-time curves were established by the sampling time midpoint as timeline. The pharmacokinetic fitting parameters were obtained by using non-compartment model. Results The LC-MS detection method was sensitive, specific, and able to meet the analytical requirements. The main pharmacokinetics parameters of normal rat after ig administration with low-, medium-, and high-dose Sal B were as follows: Cmax were (38.551 ± 6.692), (95.550 ± 12.544), and (204.251 ± 20.342) ng/mL, respectively, tmax were (1.125 ± 0.000), (1.375 ± 0.125), and (1.125 ± 0.125) h, respectively, AUC0—t were (65.995 ± 12.367), (178.806 ± 33.592), and (422.836 ± 72.344) h·ng/mL, respectively, MRT were (2.002 ± 0.061), (1.911 ± 0.042), and (1.955 ± 0.053) h, respectively; The main pharmacokinetics parameters of hyperlipidemia rats after ig administration with low-, medium- and high-dose Sal B were as follows: Cmax were (49.265 ± 7.317), (113.986 ± 15.294), and (246.454 ± 30.476) ng/mL, tmax were (1.125 ± 0.000), (1.125 ± 0.125), and (1.375 ± 0.125) h, respectively, AUC0—t were (96.013 ± 15.384), (207.192 ± 32.676), and (486.843 ± 89.276) h·ng/mL, respectively, MRT were (2.161 ± 0.049), (2.089 ± 0.033), and (2.097 ± 0.035) h, respectively. Conclusion The LC-MS method is suitable for the analysis with the high sensitivity and strong specificity. The pharmacokinetics parameters of Sal B of hyperlipidemia rats, such as Cmax, AUC0—t, and MRT, are higher than those of normal rats, which is conducive to play a therapeutic role, but without statistical significance.
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[基金项目]
国家自然科学基金项目(30701097)