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建立一种灵敏度高、重现性好的高效液相色谱-质谱法(LC-MS/MS)测定人血浆中甘草次酸的浓度,并用于甘草酸铵的人体药动学研究。采用液-液萃取法进行血浆样品预处理,色谱柱为C_(18)柱,流动相为乙腈-5mmol/L乙酸铵(70:30,v/v),流速0.8mL/min。采用负离子模式,多离子监测(MRM)方式进行检测,甘草次酸与内标甲砜霉素离子对质核比(m/z)分别为469.3→355.3、354.1→185.0。方法学验证表明此方法特异性强、灵敏度高、准确度与精密度符合要求,线性范围为0.5-500ng/mL,血浆样本经两次冻融及冷冻稳定良好,可以用于甘草酸铵的人体药代动力学研究。健康志愿者口服75mg甘草酸铵后,活性代谢产物甘草次酸的药动学参数如下:AUC_(0-t)(3457.26±1999.01)ng·h/mL、AUC_(0-∞)(3708.85±2428.36)ng·h/mL、MRT_(0-t)(19.69±4.03)h、MRT_(0-∞)(22.83±8.45)h、t_(1/2)Z(11.71±7.77)h、T_(max)(13.40±4.84)h、CLz/F(29±17±19±82)L/h、Vz/F(487.38±518.07)L、C_(max)(215.85±99.88)ng/mL。
To establish a high sensitivity and reproducibility high performance liquid chromatography-mass spectrometry (LC-MS / MS) determination of glycyrrhetic acid in human plasma concentration, and for human glycyrrhizin pharmacokinetic studies. The plasma samples were pretreated by liquid - liquid extraction. The column was C 18 column with mobile phase of acetonitrile - 5 mmol / L ammonium acetate (70:30, v / v) and flow rate of 0.8 mL / min. Negative ion mode and multi-ion monitoring (MRM) were used to detect the mass ratio (m / z) of glycyrrhetinic acid to internal standard thiamphenicol ion pair 469.3 → 355.3, 354.1 → 185.0, respectively. The methodological verification shows that the method has high specificity, high sensitivity, accuracy and precision to meet the requirements, with a linear range of 0.5-500 ng / mL. The plasma samples are stable after two freeze-thaw cycles and freezing and can be used in the human body of ammonium glycyrrhizinate Pharmacokinetic studies. Pharmacokinetic parameters of glycyrrhetic acid, the active metabolite, were as follows after oral administration of 75 mg glycyrrhizinate to healthy volunteers: AUC_ (0-t) (3457.26 ± 1999.01) ng.h / mL, AUC_0_∞ (3708.85 ± 2428.36 MRT_ (0-∞) (22.83 ± 8.45) h, t_ (1/2) Z (11.71 ± 7.77) h and T_ (max) (13.40 ± 4.84) h, CLz / F (29 ± 17 ± 19 ± 82) L / h, Vz / F (487.38 ± 518.07) L and C max (215.85 ± 99.88) ng / mL.