Open AccessHigh‐Performance Liquid Chromatography Method for Rich Pharmacokinetic Sampling Schemes in Translational Rat Toxicity Models With Vancomycin
Author(s) -
Joshi MD,
O'Donnell JN,
Venkatesan N,
Chang J,
Nguyen H,
Rhodes NJ,
Pais G,
Chapman RL,
Griffin B,
Scheetz MH
Publication year - 2017
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12484
Subject(s) - high performance liquid chromatography , chromatography , pharmacokinetics , formic acid , vancomycin , chemistry , analyte , toxicity , kidney , pharmacology , medicine , biology , organic chemistry , bacteria , genetics , staphylococcus aureus
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.