关键词: Buyang Huanwu Decoction LC-MS/MS brain pharmacokinetics cerebral ischemia microdialysis

来  源:   DOI:10.1016/j.chmed.2022.03.007   PDF(Pubmed)

Abstract:
UNASSIGNED: To conduct a comparative study on the brain pharmacokinetics of seven ingredients (i. e. senkyunolide A, ferulic acid, formononetin, calycosin, ononin, calycosin-O-β-D-glucopyranoside, and paeoniflorin), which were the compounds of Buyang Huanwu Decoction (BHD), in normal and cerebral ischemia rats administrated intragastrically with BHD.
UNASSIGNED: The samples of normal and permanent middle cerebral artery occlusion (pMCAO) rats were collected by using brain microdialysis technique. The concentrations of seven ingredients were determined by the HPLC-MS/MS method. After the BHD were administrated intragastrically to the rats for seven consecutive days, brain microdialysis probes were inserted into the hippocampus of rats, and then the brain microdialysates were collected at 20 min time intervals for 5 h. The separation of the seven ingredients and internal standard (IS) was carried out on an ACQUITY UPLC BEH C18 (2.1 mm × 100 mm, 1.7 μm) chromatographic column, using a mobile phase consisting of acetonitrile (containing 0.1% formic acid) and water (containing 0.1% formic acid) for gradient elution within 13 min. The ionization was conducted using an ESI source in positive ion mode. Multiple reaction monitoring mode was used for quantification of ingredients in BHD.
UNASSIGNED: Linearity, accuracy, precision, matrix effect and stability of LC-MS/MS method were all satisfactory, successfully applied to compare the pharmacokinetics of the analytes between normal and model rats after intragastric administration of BHD. Compared with the normal group, the model group after the administration of the BHD showed that T 1/2 of formononetin and ononin were longer, and except for calycosin-O-β-D-glucopyranoside (P < 0.01), there was no significant difference between the normal group and the model group. The C max of senkyunolide A and calycosin of model group were increased, while the T max of senkyunolide A was decreased, and except for the T max of PF, the differences between the two groups were statistically significant (P < 0.01).
UNASSIGNED: The LC-MS/MS method combined with microdialysis was successfully applied to the comparative study of brain pharmacokinetics of seven ingredients in BHD. After intragastric administration of BHD, there were differences in the pharmacokinetics of seven ingredients in the brain hippocampus between normal rats and model rats, probably related to the characteristics of the ingredients and the effects of cerebral ischemia on the absorption and distribution of the ingredients.
摘要:
UNASSIGNED:对七种成分的脑药代动力学进行比较研究(i。e.senkyunolideA,阿魏酸,福蒙素,calycosin,ononin,毛囊素-O-β-D-吡喃葡萄糖苷,和芍药苷),补阳还五汤(BHD)的化合物,在正常和脑缺血大鼠胃内给予BHD。
UNASSIGNED:使用脑微透析技术收集正常和永久性大脑中动脉闭塞(pMCAO)大鼠的样本。用HPLC-MS/MS法测定7种成分的浓度。在BHD连续7天给予大鼠胃内给药后,将脑微透析探针插入大鼠海马,然后以20分钟的时间间隔收集脑微透析液5小时。在ACQUITYUPLCBEHC18(2.1mm×100mm,1.7μm)色谱柱,使用由乙腈(含0.1%甲酸)和水(含0.1%甲酸)组成的流动相在13分钟内进行梯度洗脱。使用ESI源以正离子模式进行电离。多反应监测模式用于定量BHD中的成分。
未经评估:线性,准确度,精度,LC-MS/MS方法的基体效应和稳定性均令人满意,成功应用于比较正常和模型大鼠灌胃BHD后分析物的药代动力学。与正常组相比,BHD给药后的模型组显示,海蒙素和onenin的T1/2时间更长,除毛蒜素-O-β-D-吡喃葡萄糖苷(P<0.01)外,正常组与模型组比较差异无统计学意义。模型组senkyunolideA和calycosin的Cmax增加,当senkyunolideA的Tmax降低时,除了PF的Tmax,两组比较差异有统计学意义(P<0.01)。
UNASSIGNED:LC-MS/MS结合微透析的方法成功地应用于BHD中7种成分的脑药代动力学的比较研究。BHD灌胃后,正常大鼠和模型大鼠脑海马中7种成分的药代动力学存在差异,可能与成分的特性以及脑缺血对成分吸收和分布的影响有关。
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