黄芩苷纳米混悬剂大鼠体内药代动力学研究

Pharmacokinetics of baicalin nanosuspension in rats

关键词:  黄芩苷  纳米混悬剂  LC-MS/MS  大鼠  药代动力学

Key words:  baicalin  nanoparticle  LC-MS/MS  rat  pharmacokinetics

摘要:

[目的]建立液相色谱-质谱联用（LC-MS/MS）的方法，并对大鼠灌胃给药黄芩苷纳米混悬剂（BL-NSPS）后黄芩苷的药代动力学进行研究。[方法]采用LC-MS/MS方法，色谱柱：Waters ACQUITY UPLC^®HSS C₁₈柱（1.8 μm，2.1 mm×50 mm，美国Waters公司）；柱温：30℃；流速：0.3 mL/min；进样量：5 μL；流动相：0.1%甲酸水（A）-乙腈（B）；梯度洗脱。以卡马西平为内标，采用电喷雾离子源（ESI离子源），在正离子检测方式下进行多反应离子监测（MRM），检测离子对分别为m/z 447.09→270.80（黄芩苷）、m/z 237.10→193.80（卡马西平，内标），测定大鼠灌胃给药BL-NSPS后黄芩苷的血药浓度，并用WinNonlin 6.0版药动学软件计算其药代动力学参数。[结果]黄芩苷在24.75~4 950.00 ng/mL范围内线性关系良好，血浆中内源性物质无干扰，LC-MS/MS方法回收率、基质效应、精密度、准确度和稳定性均符合生物样品的测定要求。BL-NSPS和黄芩苷原料药（BL-Bulk）的C_max分别为（3 329.10±499.10）ng/mL、（1 257.84±158.21）ng/mL。BL-NSPS的C_max较BL-Bulk有了显著提高（P<0.05），BL-NSPS的相对生物利用度为（160.97±47.78）%。[结论]建立的LC-MS/MS测定方法准确度强、专属性好，可用于黄芩苷的药代动力学研究。结果显示，BL-NSPS能增加药物的吸收速率，缩短了药物起效时间，提高药物体内生物利用度，可为黄芩苷制剂的进一步研发奠定基础。

Abstract:

[Objective] To establish a liquid chromatography-mass spectrometry (LC-MS/MS) method to evaluate its pharmacokinetics in rats.[Methods] ALC-MS/MS method that column of Waters ACQUITY UPLC-HSS C₁₈(1.8 μm, 2.1 mm×50 mm)and a mixture of 0.1% formic acid water solution (A)-acetonitrile (B) as the mobile phase at the flow-rate of 0.3 mL/min, the column temperature was 30℃ and the injection volume was 5 μL. Carbamazepine was used as the internal standard, detection was by postive ion electrospray ionization (ESI) mass spectrometry with multiple-reaction monitoring (MRM). Detection of ion pairs respectively are m/z 447.09→270.80 for baicalin, m/z 237.10→193.80 for carbamazepine employed to determine the concentration of baicalin in plasma by oral administration in rats and the pharmacokinetics software of WinNonlin version 6.0 was used to calculate the pharmacokinetics parameters.[Results] The linear calibration curves were obtained over the concentration range 24.75~4 950.00 ng/mL. Endogenous substances in the plasma did not interfere with the determination, the recovery rate, matrix effect, precision, accuracy and stability of the method are in accordance with the requirements of biological samples. The C_max of BL-NSPS and BL-Bulk were (3 329.10±499.10) ng/mL and (1 257.84 ±158.21) ng/mL, respectively. The C_max of BL-NSPS was significantly higher than that of BL-Bulk (P<0.05), and the relative bioavailability of BL-NIPS was (160.97±47.78)%.[Conclusion] The LC-MS/MS method has high accuracy and specificity, and can be used to detect the pharmacokinetics of baicalin. What's more, the experimental results show that baicalin nanosuspensions can increase the absorption rate of drugs, shorten the onset time of the drugs, improve the bioavailability of the drug in vivo and lay a foundation for the further development of baicalin preparation.