LC/MS/MS measurement of gentamicin in bovine plasma, urine, milk, and biopsy samples taken from kidneys of standing animals

Heller, David; Peggins, James O.; Nochetto, Cristina; Smith, Michelle; Chiesa, O. A.; Moulton, Keesla

doi:10.1016/j.jchromb.2005.04.015

Cited by 78 publications

(48 citation statements)

References 12 publications

(21 reference statements)

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“…A portion was removed for protein content determination by the methods of Bradford et al [23] and samples were centrifuged at 4⁰C for 5min at 14,000rpm. Intracellular gentamicin was detected by LC-MS/MS in multiple-reaction monitoring mode (MRM) with the main working parameters and product ion scanning based on methods described previously [24]. Analyses were performed using an Applied Biosystems/MDS Sciex Coefficient of variation calculated from 5 standard curves ran on 5 separate days was <10%…”

Section: Gentamicin Intracellular Quantification By Lc-ms/msmentioning

confidence: 99%

Statins inhibit aminoglycoside accumulation and cytotoxicity to renal proximal tubule cells

Antoine¹,

Srivastava²,

Pirmohamed³

et al. 2010

Biochemical Pharmacology

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International audienceNephrotoxicity due to renal proximal tubule accumulation of aminoglycoside (AG) antibiotics, such as gentamicin, represents a major clinical problem. Receptor-mediated endocytosis via the multi-ligand receptor megalin is thought to be a key mechanism in the cellular uptake of AGs and nephrotoxicity. This process can be modulated by the intracellular concentration of isoprenoid pyrophosphates derived from the processing of mevalonate by 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Post-translation modifications by isoprenoid pyrophosphates are necessary for GTP-binding protein function. Given that statins inhibit HMG-CoA reductase and therefore affect the concentration of isoprenoid pyrophosphates, we have tested the hypothesis that statins will lead to a reduction in AG renal proximal tubule accumulation and cytotoxicity. Gentamicin accumulated within cultured proximal tubule derived opossum kidney (OK) cells and led to dose- and time-dependent cell death which was inhibited by non-toxic doses of simvastatin (IC 1.3μM), rosuvastatin (IC 16.3μM) and pravastatin (IC 38.8μM). The mechanism of inhibition was linked to the degree of cholesterol synthesis inhibition and GTP-binding protein unprenylation. Moreover, co-incubation with mevalonate or geranyl-geranyl pyrophosphate, products of HMG-CoA reductase, reversed the inhibitory effect of statins on cellular accumulation and cytotoxicity of gentamicin. In summary, our data suggest that the inhibition of the mevalonate pathway by statins may provide a potential therapeutic strategy to prevent AG-induced nephrotoxicity

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Section: Gentamicin Intracellular Quantification By Lc-ms/msmentioning

confidence: 99%

Statins inhibit aminoglycoside accumulation and cytotoxicity to renal proximal tubule cells

Antoine¹,

Srivastava²,

Pirmohamed³

et al. 2010

Biochemical Pharmacology

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“…These methods used liquid chromatography/tandem mass spectrometry (LC/MS/MS) to measure penicillin concentrations to fairly low levels. 1 These methods were applied to the tissue-fluid correlation studies mentioned above. 2 A novel laparoscopic surgical technique was used to obtain kidney cortex samples from standing animals.…”

mentioning

confidence: 99%

Detection of penicillin residues in bovine oral fluid (saliva) by liquid chromatography/tandem mass spectrometry

Heller¹,

Smith²,

Chiesa³

2005

Rapid Comm Mass Spectrometry

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“…A gradient separation was achieved for vancomycin with a starting A:B ratio of 100:0 at a flow rate of 0.3 mL/minute. The described conditions for gentamicin were used by Heller et al [18], where the coeluted gentamicin components C1, C2, C2a and C1a were detected simultaneously. The apparatus used for detection of all three antibiotics was an API 4000 QTrap (Applied Biosystems, Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

Sufficient Release of Antibiotic by a Spacer 6 Weeks after Implantation in Two-stage Revision of Infected Hip Prostheses

Fink

Vogt

Reinsch

et al. 2011

Clinical Orthopaedics &Amp; Related Research

105

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Background Although antibiotic-loaded spacers are commonly used to treat periprosthetic infections, it is unclear whether spacers continue to release bactericidal levels of antibiotic 6 weeks after implantation. Questions/purposes We asked whether an antibiotic can be detected in the tissue surrounding the spacer 6 weeks after implantation and whether the concentration is higher than the minimal inhibition concentration (MIC) previously determined for pathogens that are responsible for most periprosthetic infections. Methods We removed 14 spacers used in two-stage septic revisions of infected hip prostheses 6 weeks after the primary implantations and determined the concentration of the antibiotics in the membrane formed between the spacer and the neighboring bone on the acetabular and the femoral sides. In seven cases Copal cement with gentamicin and clindamycin were used, and in seven other cases vancomycin was added to the Copal cement. Concentrations of the spacer antibiotics in the neighboring tissue were determined by tandem mass spectroscopy. Results All three antibiotics were detected in concentrations higher than their MIC. There were no differences between the groups regardless whether vancomycin was added to the cement, or whether the cement was applied with the acetabular cup spacer or with the stem spacer. Conclusions We concluded that, using the spacer technique described in this study, 6 weeks after spacer implantation, the concentrations of antibiotic are sufficient to treat a periprosthetic infection.

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LC/MS/MS measurement of gentamicin in bovine plasma, urine, milk, and biopsy samples taken from kidneys of standing animals

Cited by 78 publications

References 12 publications

Statins inhibit aminoglycoside accumulation and cytotoxicity to renal proximal tubule cells

Statins inhibit aminoglycoside accumulation and cytotoxicity to renal proximal tubule cells

Detection of penicillin residues in bovine oral fluid (saliva) by liquid chromatography/tandem mass spectrometry

Sufficient Release of Antibiotic by a Spacer 6 Weeks after Implantation in Two-stage Revision of Infected Hip Prostheses

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