磷丙泊酚二钠及其活性代谢产物在妊娠大鼠体内的药代动力学研究

Pharmacokinetics of fospropofol disodium and its active metabolites in pregnant rats

目的考察磷丙泊酚二钠及其活性代谢产物丙泊酚在妊娠大鼠体内的药代动力学特征。方法建立同时检测SD大鼠血浆中磷丙泊酚二钠和丙泊酚浓度的高效液相色谱串联质谱(LC-MS/MS)分析方法并进行方法学考察。妊娠SD大鼠静脉给予120 mg·kg^(-1)磷丙泊酚二钠,分别于给药前及给药后3、6、10、15、30、45、60、90、120、150 min眼内眦取血,用LC-MS/MS法测定血浆药物浓度,用DAS软件计算磷丙泊酚二钠和丙泊酚的药代动力学参数。结果磷丙泊酚二钠和丙泊酚的标准曲线方程分别为y=0.77x+0.08(r=0.9972)和y=8.90×10^(-3)x+4.70×10^(-3)(r=0.9971),线性范围分别为0.2~250.0μg·mL^(-1)和1.0~80.0μg·mL^(-1)。磷丙泊酚二钠静脉给药后,丙泊酚t_(max)为(9.50±3.33)min,磷丙泊酚二钠和丙泊酚的C_(max)分别为(349.50±154.10)和(28.33±15.30)μg·mL^(-1),t_(1/2)分别为(24.35±11.33)和(43.87±4.86)min,AUC_(0→t)分别为(79.40±21.53)和(25.13±15.71)μg·mL^(-1)·h。结论本实验建立的LC-MS/MS方法可以同时测定大鼠血浆中磷丙泊酚二钠和丙泊酚浓度,妊娠大鼠静脉给予磷丙泊酚二钠后可以很快转化为活性代谢产物丙泊酚来发挥作用。

Objective To investigate the pharmacokinetics of fospropofol disodium and its active metabolite propofol in pregnant rats.Methods A liquid chromatography tandem mass spectrometry(LC-MS/MS)method for simultaneous determination of fospropofol disodium and propofol in plasma of SD rats was establish and investigated methodologically.Pregnant SD rats were given 120 mg·kg^(-1) fospropofol disodium intravenously,and blood was taken from the inner canthus before administration and 3,6,10,15,30,45,60,90,120,150min after administration.Plasma drug concentration was determined by LC-MS/MS method,and pharmacokinetic parameters of fospropofol disodium and propofol were calculated by DAS software.Results The standard curve equations of fospropofol disodium and propofol were y=0.77x+0.08(r=0.9972)and y=8.90×10^(-3)x+4.70×10^(-3)(r=0.9971),and the linear ranges were 0.2-250.0μg·mL^(-1) and 1.0-80.0μg·mL^(-1).After intravenous administration of fospropofol disodium,the t_(max) of propofol was(9.50±3.33)min,the C_(max) of fospropofol disodium and propofol were(349.50±154.10)and(28.33±15.30)μg·mL^(-1),t_(1/2) wa s(24.35±11.33)and(43.87±4.86)min,and AUC_(0→t) were(79.40±21.53)and(25.13±15.71)μg·mL^(-1)·h.Conclusion The LC-MS/MS method established in this study can simultaneously determine the concentration of fospropofol disodium and propofol in plasma of rats,and fospropofol disodium can also be quickly converted into active metabolite propofol after intravenous administration to pregnant rats.