High‐Performance Liquid Chromatography Method for Rich Pharmacokinetic Sampling Schemes in Translational Rat Toxicity Models With Vancomycin

Joshi,; O'Donnell, J. Nicholas; Venkatesan, Natarajan; Chang, Jack; Nguyen, Hoang Anh; Rhodes, Nathaniel J.; Pais, Gwendolyn; Chapman, RL; Griffin, Brooke; Scheetz, Marc H.

doi:10.1111/cts.12484

Cited by 11 publications

(6 citation statements)

References 38 publications

(84 reference statements)

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“…Plasma concentrations of vancomycin were quantified with LC and column conditions similar to our previous report, 17,23 with the following notable changes to transfer the method to LC-MS/MS. A plasma sample volume of 40 mL was combined with 4 mL of the internal standard of polymyxin B at a concentration of 0.1 mg/mL.…”

Section: Determination Of Vancomycin Concentrations In Plasmamentioning

confidence: 99%

Twenty-four hour pharmacokinetic relationships for intravenous vancomycin and novel urinary biomarkers of acute kidney injury in a rat model

Avedissian

Pais

O'Donnell

et al. 2019

Journal of Antimicrobial Chemotherapy

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Objectives To identify the pharmacokinetic (PK) and toxicodynamic (TD) relationship for vancomycin-induced kidney injury. Methods Male Sprague–Dawley rats received intravenous (iv) vancomycin. Doses ranging from 150 mg/kg/day to 400 mg/kg/day were administered as a single or twice-daily injection over 24 h (total protocol duration). Controls received iv saline. Plasma was sampled with up to eight samples in 24 h per rat. Twenty-four hour urine was collected and assayed for kidney injury molecule 1 (KIM-1), osteopontin and clusterin. Vancomycin in plasma was quantified via LC-MS/MS. PK analyses were conducted using Pmetrics for R. PK exposures during the first 24 h (i.e. AUC0–24h, Cmax 0–24h and Cmin 0–24h) were calculated. PK/TD relationships were assessed with Spearman’s rank coefficient (rs) and the best-fit mathematical model. Results PK/TD data were generated from 45 vancomycin-treated and 5 control rats. A two-compartment model fit the data well (Bayesian: observed versus predicted R2 = 0.97). Exposure–response relationships were found between AUC0–24h versus KIM-1 and osteopontin (R2 = 0.61 and 0.66) and Cmax 0–24h versus KIM-1 and osteopontin (R2 = 0.50 and 0.56) using a four-parameter Hill fit. Conversely, Cmin 0–24h was less predictive of KIM-1 and osteopontin (R2 = 0.46 and 0.53). A vancomycin AUC0–24h of 482.2 corresponded to a 90% of maximal rise in KIM-1. Conclusions Vancomycin-induced kidney injury as defined by urinary biomarkers is driven by vancomycin AUC or Cmax rather than Cmin. Further, an identified PK/TD target AUC0–24h of 482.2 mg·h/L may have direct relevance to human outcomes.

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Section: Determination Of Vancomycin Concentrations In Plasmamentioning

confidence: 99%

Twenty-four hour pharmacokinetic relationships for intravenous vancomycin and novel urinary biomarkers of acute kidney injury in a rat model

Avedissian

Pais

O'Donnell

et al. 2019

Journal of Antimicrobial Chemotherapy

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“…Thus, vancomycin washout periods were shorter for the rats dosed during later trimesters (T3 Ͼ T2 Ͼ T1) and may have contributed to the increased vancomycin levels detected in the kidneys of rats dosed in later trimesters. We ran all the kidney homogenate samples on high-performance liquid chromatography (HPLC) first with our previously reported method (16) and later on LC-MS/MS. The HPLC results are in agreement with LC-MS/MS analysis.…”

Section: Discussionmentioning

confidence: 99%

“…LC-MS/MS method. Plasma and kidney concentrations of vancomycin were quantified with LC and column conditions as described in our previous reports (16,43), using the sample preparation techniques as mentioned above to transfer the method to LC-MS/MS. Following centrifugation, 2 l of the supernatant was injected into an Agilent 1260 LC attached to an Agilent 6420 triple quadrupole.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Fetal and Maternal Vancomycin-Induced Kidney Injury during Pregnancy in a Rat Model

Joshi

Pais

Chang

et al. 2019

Antimicrob Agents Chemother

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Previous literature suggests that maternal vancomycin crosses the placental barrier to the fetus. Further, early animal studies indicated that kidney injury was not observed in the progeny. These studies were conducted prior to the availability of sensitive biomarkers for kidney injury. Therefore, a previous finding of no renal damage to the infant may be misleading. Vancomycin was administered intravenously to pregnant rats at a dose of 250 mg/kg of body weight/day (N = 6 per trimester) on three consecutive gestational days (GD) during trimesters 1, 2, and 3 (T1, T2, and T3, respectively) in three independent cohorts. The dams carried to term and delivered vaginally on GD 21. Kidneys were harvested from dams and pups and homogenized. Samples were prepared by protein precipitation and injected in a liquid chromatography tandem mass spectrometer, and vancomycin was quantified. The kidney tissue homogenate from dams and pups were analyzed for kidney injury molecule-1 (KIM-1). As trimesters progressed, the quantity of vancomycin increased linearly in the kidneys of both rat dams and pups (P < 0.0001 for T1 and T3, P < 0.0001 for T2 and T3, and P < 0.0001 for T3 and T3 control for both rat dams and pups). KIM-1 concentrations in pup kidneys were significantly higher when dams were administered vancomycin in trimesters 1 (P = 0.0001) and 2 (P = 0.0024) than in controls in trimester 3. Data demonstrate persistence of vancomycin in maternal and rat pup kidneys in all three trimesters of pregnancy with associated damage to the kidney, as indicated by expression of KIM-1.

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“…Various methods for determining VAN using different techniques have been described in the literature, spectrofluorimetry 3,4 , UVspectrophotometry [5][6][7][8] , IR-spectrometry 9 , electrochemical detection 10 , flow injection spectrometry [11][12][13] , solid phase extraction including adsorbents magnetic nanoparticles 14 , LC-MS spectroscopy 15 , spectrophotometric oxidation methods [16][17] and high performance liquid chromatography methods [18][19][20] . Most of the methods described above are sensitive but require expensive instrumentation and time consuming.…”

Section: Figure 1 Structure Of Vancomycin Hclmentioning

confidence: 99%

Spectrophotometric Analysis of Vancomycin Hydrochloride in Pure and Pharmaceutical Injections via Batch and Cloud Point Extraction Techniques

2023

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Development of a precise and delicate reaction has been acquired for the determination of vancomycin hydrochloride using batch and cloud point extraction (CPE) methods. The first method is based on the formation of azo dye as a result of diazotized dapsone coupled with vancomycin HCl (VAN) in a basic medium. The sensitivity of this reaction was enhanced by utilizing a nonionic surfactant (Triton X-114) and the cloud point extraction technique (second method). The azo dye formed was extracted into the surfactant-rich phase, dissolved in ethanol and detected at λ max 446 nm spectrophotometrically. The reaction was investigated using both batch and CPE methods (with and without extraction), and a simple comparison between the two developed methods was made. The conditions that affect the extraction process and the sensitivity of the methods have been carefully examined. The linearity of the calibration curves was in the range of 3-50 and 0.5-25 µg.mL -1 with limits of detection of 0.806 and 0.214 µg.mL -1 for VAN in both batch and CPE procedures, respectively. The percentage of relative standard deviation (R.S.D.%) for the two methods was better than 2.54% and 2.83%, respectively. The recommended procedures have been effectively used to assay VAN in commercial injections.

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High‐Performance Liquid Chromatography Method for Rich Pharmacokinetic Sampling Schemes in Translational Rat Toxicity Models With Vancomycin

Cited by 11 publications

References 38 publications

Twenty-four hour pharmacokinetic relationships for intravenous vancomycin and novel urinary biomarkers of acute kidney injury in a rat model

Twenty-four hour pharmacokinetic relationships for intravenous vancomycin and novel urinary biomarkers of acute kidney injury in a rat model

Evaluation of Fetal and Maternal Vancomycin-Induced Kidney Injury during Pregnancy in a Rat Model

Spectrophotometric Analysis of Vancomycin Hydrochloride in Pure and Pharmaceutical Injections via Batch and Cloud Point Extraction Techniques

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