High‐Performance Liquid Chromatography Method for Rich Pharmacokinetic Sampling Schemes in Translational Rat Toxicity Models With Vancomycin. Issue 6 (4th July 2017)

• Record Type: Journal Article
• Authors: Joshi, MD; O'Donnell, JN; Venkatesan, N; Chang, J; Nguyen, H; Rhodes, NJ; Pais, G; Chapman, RL; Griffin, B; Scheetz, MH
• Is Part Of: Clinical and translational science. Volume 10:Issue 6(2017)
• Page Start: 496
• Page End: 502
• Publication Date: 2017-07-04
• Subjects: Medicine, Experimental -- Periodicals; Medical innovations -- Periodicals; 616.027
• DOI: 10.1111/cts.12484
• Languages: English
• ISSNs: 1752-8054

Abstract

Abstract: 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.