高效液相色谱法用于研究万古霉素在大鼠毒性模型中的丰富药代动力学采样方案。
High-Performance Liquid Chromatography Method for Rich Pharmacokinetic Sampling Schemes in Translational Rat Toxicity Models With Vancomycin.
机构信息
Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA.
Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA.
出版信息
Clin Transl Sci. 2017 Nov;10(6):496-502. doi: 10.1111/cts.12484. Epub 2017 Jul 4.
A translational need exists to understand and predict vancomycin-induced kidney toxicity. We describe: (i) a vancomycin high-performance liquid chromatography (HPLC) method for rat plasma and kidney tissue homogenate; (ii) a rat pharmacokinetic (PK) study to demonstrate utility; and (iii) a catheter retention study to enable future preclinical studies. Rat plasma and pup kidney tissue homogenate were analyzed via HPLC for vancomycin concentrations ranging from 3-75 and 15.1-75.5 μg/mL, respectively, using a Kinetex Biphenyl column and gradient elution of water with 0.1% formic acid: acetonitrile (70:30 v/v). Sprague-Dawley rats (n = 10) receiving 150 mg/kg of vancomycin intraperitoneally had plasma sampled for PK. Finally, a catheter retention study was performed on polyurethane catheters to assess adsorption. Precision was <6.1% for all intra-assay and interassay HPLC measurements, with >96.3% analyte recovery. A two-compartment model fit the data well, facilitating PK exposure estimates. Finally, vancomycin was heterogeneously retained by polyurethane catheters.
需要对万古霉素诱导的肾毒性进行理解和预测，因此我们描述了：（i）一种用于大鼠血浆和肾脏组织匀浆的万古霉素高效液相色谱（HPLC）方法；（ii）一项大鼠药代动力学（PK）研究，以证明该方法的实用性；（iii）一项留置导管研究，以支持未来的临床前研究。大鼠血浆和幼鼠肾脏组织匀浆分别通过 HPLC 进行分析，万古霉素浓度范围分别为 3-75μg/mL 和 15.1-75.5μg/mL，采用 Kinetex 联苯柱，水与 0.1%甲酸：乙腈（70:30v/v）梯度洗脱。10 只接受 150mg/kg 万古霉素腹膜内注射的 Sprague-Dawley 大鼠进行 PK 采样。最后，对聚氨酯导管进行留置导管研究以评估吸附情况。所有 HPLC 测量的日内和日间精密度均<6.1%，分析物回收率>96.3%。两室模型很好地拟合了数据，有助于进行 PK 暴露评估。最后，万古霉素被聚氨酯导管不均匀地保留。
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