灯盏乙素在兔体内药代动力学

目的建立测定灯盏乙素血浆浓度的固相萃取-高效液相色谱（SPE-HPLC）法,并研究家兔iv灯盏花素的药代动力学。方法采用甲醇-水-磷酸为流动相，Nucleosil C₁₈色谱柱为固定相,紫外检测波长335 nm,外标法定量。给家兔分别iv灯盏花素10,20和40 mg·kg^-1,SPE-HPLC法检测血浆药物浓度。结果线性范围0.02～10.0 mg·L^-1,最低检测浓度0.02 mg·L^-1,方法回收率96.15%～99.31%,日内、日间RSD值均小于10%。家兔iv灯盏花素时,灯盏乙素血浆浓度变化符合三房室模型。灯盏乙素低、中剂量组的主要药代动力学参数无显著性差异,而高剂量组与低、中剂量组比较差异显著。结论该法准确、灵敏、简便,适用于灯盏乙素血浆浓度的测定。灯盏花素经兔iv后的药代动力学符合三房室模型，剂量为10～20 mg·kg^-1时,药物的体内变化为线性动力学过程,而40 mg·kg^-1时未表现线性动力学特征。

Study on pharmacokinetics of scutellarin in rabbits

Aim To establish a solid phase extraction-high performance liquid chromatographic (SPE-HPLC) method for determining plasma scutellarin concentration, and study its pharmacokinetics after iv breviscapine in rabbits. Methods Methanol-water-phosphoric acid (50∶50∶0.5) mixture was used as mobile phase, Nucleosil C18 column (250 mm×4.6 mm ID) was selected. The wavelength of UV detection was 335 nm. Fifteen rabbits, randomized into 3 groups, were given breviscapine iv at the dose of 10, 20 and 40 mg*kg-1. Scutellarin in plasma was determined by SPE-HPLC method. Results Linearity was obtained over the range of 0.02-10.0 mg*L-1 of scutellarin. The method recovery was 96.15%-99.31%; the within-day and between-day RSDs were all below 10%. After iv 10, 20 and 40 mg*kg-1 of breviscapine to rabbits, the concentration-time curve of scutellarin fitted to a three compartment model. The main pharmacokinetic parameters showed no significant difference between low and medium doses, but the difference was significant between high dose and other doses. Conclusion This assay method was accurate, sensitive, simple and suitable for the measurement of plasma scutellarin concentration. The pharmacokinetic characteristics were found to fit a three-compartment model following iv injection of breviscapine to rabbits. The changes of drug concentration in vivo exhibited linear kinetics over the dosage range of 10-20 mg*kg-1, but when the dosage was 40 mg*kg-1, the linear kinetic properties disappeared.