Development and validation of an ultra-high performance liquid chromatography–tandem mass spectrometry method for the simultaneous determination of iohexol, p-aminohippuric acid and creatinine in porcine and broiler chicken plasma

Dhondt, Laura; Croubels, Siska; Cock, Pieter De; Paepe, Peter De; Baere, Siegrid De; Devreese, Mathias

doi:10.1016/j.jchromb.2019.04.017

Cited by 17 publications

(13 citation statements)

References 43 publications

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“…Therefore, 0.5% of formic acid in water/methanol (80/20, v / v ) was applied as the extraction solvent for NCG in the feeds (Figure 3). For the animal samples, the biggest interference came from the high lipid and protein content in the samples [21]. Similarly, different proportions of methanol and 0.5% of formic acid solution were also tested for the optimization of extraction agents.…”

Section: Resultsmentioning

confidence: 99%

Determination of N-Carbamylglutamate in Feeds and Animal Products by High Performance Liquid Chromatography Tandem Mass Spectrometry

Zeng

Kong

et al. 2019

Molecules

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N-carbamylglutamate (NCG), a synthetic analogue of N-acetylglutamate, is an activator of blood ammonia conversion and endogenous arginine synthesis. Here, we established an accurate quantitative determination of NCG in feeds, animal tissues, and body fluids using the high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The sample pretreatment procedures included extraction with 0.5% of formic acid in water/methanol (80/20, v/v), and purification using an anionic solid phase extraction cartridge. Satisfactory separation of NCG was achieved in 20 min with the application of an Atlantis T3 column, and a confirmative detection of NCG was ensured by multiple reaction monitoring of positive ions. NCG spiked in feeds, tissues, and body fluids were evaluated in regard to linearity, sensitivity, recovery, and repeatability. Recoveries for different sample matrices were in the range of 88.12% to 110.21% with relative standard deviations (RSDs) less than 8.8%. Limits of quantification were within the range of 0.012 to 0.073 mg kg−1 and 0.047 to 0.077 μg mL−1 for solid and liquid samples, respectively. This study will provide a solid foundation for the evaluation of availability and metabolic mechanism of NCG in animals.

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Section: Resultsmentioning

confidence: 99%

Determination of N-Carbamylglutamate in Feeds and Animal Products by High Performance Liquid Chromatography Tandem Mass Spectrometry

Zeng

Kong

et al. 2019

Molecules

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“…Sampling points overlapped with those of IBU and were taken right before administration and 5, 10, 30, 60 min and 2, 3, 6, and 8 h after administration. Determination of iohexol and PAH in porcine plasma was performed using a validated UHPLC-MS/MS method (Dhondt et al, 2019). A more detailed description of this analytical method is given in the Supplementary Material.…”

Section: Methodsmentioning

confidence: 99%

Developmental Pharmacokinetics and Safety of Ibuprofen and Its Enantiomers in the Conventional Pig as Potential Pediatric Animal Model

et al. 2019

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Pediatric drug development, especially in disease areas that only affect children, can be stimulated by using juvenile animal models not only for general safety studies, but also to gain knowledge on the pharmacokinetic and pharmacodynamic properties of the drug. Recently, the conventional growing piglet has been suggested as juvenile animal model. However, more studies with different classes of drugs are warranted to make a thorough evaluation whether the juvenile pig might be a suitable preclinical animal model. Ibuprofen is one of the most widely used non-steroidal anti-inflammatory drugs in human. The present study determined the PK parameters, gastro-intestinal and renal safety of 5 mg/kg BW ibuprofen after single intravenous, single oral and multiple oral administration to each time eight pigs (four males, four females) aging 1, 4, 8 weeks and 6–7 months. Oral administration was performed via a gastrostomy button. A jugular catheter was used for intravenous administration and blood sampling. To assess NSAID induced renal toxicity, renal function was evaluated using iohexol and p -aminohippuric acid as markers for glomerular filtration rate and renal plasma flow, respectively. After the trial, necropsy and histology was performed to evaluate macroscopic and microscopic gastro-intestinal as well as renal lesions. Both enantiomers, R-ibuprofen and S-ibuprofen, were determined in plasma using an in-house developed and validated UHPLC-MS/MS method. Pharmacokinetic parameters were estimated using compartmental analysis. Clearance and volume of distribution of total ibuprofen and both enantiomers increased with age as was observed in human. The rate of stereochemical conversion decreased with age. Multiple oral dosing decreased the absolute oral bioavailability and maximum plasma concentration of R-ibuprofen and food consumption did not influence drug absorption. Based on the limited available pediatric literature, the current study might suggest the conventional pig as suitable animal model to evaluate NSAIDs for pediatric use.

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“…Total plasma iohexol and PAH concentrations were quantified simultaneously using a validated ultrahigh performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method as previously described by Dhondt et al (2019) (Dhondt et al, 2019). The lower limit of quantification (LLOQ) was 0.25 μg/ml for both compounds.…”

Section: Quantification Of the Renal Markersmentioning

confidence: 99%

Conventional Pig as Animal Model for Human Renal Drug Excretion Processes: Unravelling the Porcine Renal Function by Use of a Cocktail of Exogenous Markers

et al. 2020

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Over recent years, pigs have been promoted as potential animal model due to their anatomical and physiological similarities with humans. However, information about the contribution of distinct renal elimination processes [glomerular filtration rate (GFR), effective renal plasma flow (ERPF), tubular secretion, and reabsorption] in pigs is currently limited. Therefore, a cocktail of renal markers, consisting of iohexol (GFR), para-aminohippuric acid (ERPF and net tubular anion secretion), pindolol (net tubular cation secretion), and fluconazole (net tubular reabsorption) was administered intravenously to 7-week-old male conventional pigs. Plasma and urinary concentrations were determined using validated analytical methods. The clearance of iohexol (GFR) was 97.87 ± 16.05 ml/min/m² (mean ± SD). The ERPF, calculated as the renal clearance of PAH, was 226.77 ± 62.45 ml/min/m², whereas the net tubular secretion of PAH was 130.28 ± 52.62 ml/min/m². The net tubular secretion of R-pindolol and S-pindolol was 13.53 ± 12.97 and 18.01 ± 39.23 ml/min/m², respectively. The net tubular reabsorption of fluconazole was 78.32 ± 13.52 ml/min/m². Overall, this cocktail of renal markers was considered to be safe for use in pigs since no adverse effects were observed. Iohexol, PAH and fluconazole were considered suitable renal marker to assess the porcine renal function. Pindolol seems less appropriate due to the high degree of nonrenal clearance in pigs. The values of GFR, ERPF, and anion secretion are within the same range for both human and pig. Regarding the tubular reabsorption of fluconazole, slightly higher values were obtained for pigs. Nevertheless, these results indicate the conventional pig could be an appropriate animal model to study renal drug elimination processes in humans.

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Development and validation of an ultra-high performance liquid chromatography–tandem mass spectrometry method for the simultaneous determination of iohexol, p-aminohippuric acid and creatinine in porcine and broiler chicken plasma

Cited by 17 publications

References 43 publications

Determination of N-Carbamylglutamate in Feeds and Animal Products by High Performance Liquid Chromatography Tandem Mass Spectrometry

Determination of N-Carbamylglutamate in Feeds and Animal Products by High Performance Liquid Chromatography Tandem Mass Spectrometry

Developmental Pharmacokinetics and Safety of Ibuprofen and Its Enantiomers in the Conventional Pig as Potential Pediatric Animal Model

Conventional Pig as Animal Model for Human Renal Drug Excretion Processes: Unravelling the Porcine Renal Function by Use of a Cocktail of Exogenous Markers

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