Characterization of Tepoxalin and Its Related Compounds by High-Performance Liquid Chromatography/Mass Spectrometry

Burinsky, David J.; Armstrong, Barbara L.; Oyler, Alan R.; Dunphy, Richard

doi:10.1021/js9503035

Cited by 8 publications

(3 citation statements)

References 16 publications

(11 reference statements)

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“…Plasma concentrations of tepoxalin and its active metabolite, RWJ 20142, were determined by use of validated high‐performance liquid chromatography/mass spectroscopy (HPLC/MS) assay (Burinsky et al. , 1996; Waldman et al.…”

Section: Pharmacokinetic Parameters Of Tepoxalin (10 Mg/kg) After Onmentioning

confidence: 99%

Single and multiple‐dose pharmacokinetics of tepoxalin and its active metabolite after oral administration to rabbits (Oryctolagus cuniculus)

Pollock¹,

Carpenter²,

Koch

et al. 2008

Vet Pharm & Therapeutics

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The anti-inflammatory agent, tepoxalin, was administered to eight healthy 6-month-old female New Zealand white rabbits once daily at an oral dose of 10 mg/kg. Blood samples were obtained immediately before and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 h postadministration on days 1 and 10. Tepoxalin and its active metabolite, RWJ 20142, concentrations were determined in plasma by use of high-performance liquid chromatography with mass spectrometry. C(max) of the parent compound was reached between 3 and 8 h of drug administration, with a harmonic mean t(1/2) of 3.6 h. Peak tepoxalin plasma concentrations were 207 +/- 49 ng/mL. After oral administration, the metabolite RWJ 20142 achieved C(max) in plasma 2-8 h after administration, with a t(1/2) of 1.9-4.8 h (harmonic mean 2.8 h). Peak plasma concentrations of RWJ 20142 on day 1 were 2551 +/- 1034 ng/mL.

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Section: Pharmacokinetic Parameters Of Tepoxalin (10 Mg/kg) After Onmentioning

confidence: 99%

Single and multiple‐dose pharmacokinetics of tepoxalin and its active metabolite after oral administration to rabbits (Oryctolagus cuniculus)

Pollock¹,

Carpenter²,

Koch

et al. 2008

Vet Pharm & Therapeutics

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show abstract

“…After a 1‐week acclimation period, tepoxalin was administered via oral gavage or subcutaneous injection at 40 mg/kg, and non‐tumour‐bearing mice were terminally bled at specified time points following administration. Plasma was prepared for LC/MS/MS and analyzed similarly to Burinsky et al 33 with minor changes. Briefly, 5 ng of internal standard (trazadone) was added to mouse plasma.…”

Section: Methodsmentioning

confidence: 99%

Induction of VEGF by tepoxalin does not lead to increased tumour growth in a canine osteosarcoma xenograft

Sottnik

Hansen

Gustafson

et al. 2010

Vet Comparative Oncology

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The purpose of this study was to determine the impact of the non-steroidal anti-inflammatory drug tepoxalin on canine tumour cell growth and describe the changes associated with tepoxalin treatment. In vitro experiments were performed to assess tepoxalin-associated alterations in tumour cell growth. Clinically achievable tepoxalin concentrations did not significantly alter tumour cell growth in vitro. Vascular endothelial growth factor (VEGF) production and hypoxia-inducible factor-1α dose-dependently increased in vitro in the presence of tepoxalin. A canine osteosarcoma xenograft was used to determine in vivo effects of tepoxalin on tumour growth and angiogenesis. Despite increased VEGF in vitro, there was a significant growth delay associated with tepoxalin treatment. Normal dogs were administered tepoxalin to assess effects on systemic VEGF production, but not found to have significantly increased VEGF. These data suggest that tepoxalin may moderately inhibit tumour growth and may be administered as an analgesic to tumour-bearing dogs.

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“…few years. Dimers as bulk drug impurities (Mistry et al, 1997) and as degradates (Burinsky et al, 1996;Skibic et al, 1993) in pre-formulation studies have been characterized by on-line LC-MS techniques. For some drugs, dimerization has become one of the major concerns of formulation stability.…”

Section: Dimerizationmentioning

confidence: 99%

The use of liquid chromatography-mass spectrometry for the identification of drug degradation products in pharmaceutical formulations

2000

Biomed. Chromatogr.

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Recent applications of LC-MS in the analysis of drug degradation products in pharmaceutical formulations are reviewed. Drug degradation products are categorized according to their formation mechanism: oxidation, hydrolysis, dimerization and adduct formation with excipients and packaging materials. The oxidative ring opening and dimerization of an indole derivative are discussed in detail. The examples used in this review clearly demonstrate that LC-MS is a very powerful technique for the analysis of low-level degradates in formulations without the time-consuming isolation process. At the same time, limitations and precaution of using LC-MS techniques for unknown identification are also addressed. In some cases, the LC-MS data could become misleading if the ionization process and gas-phase behavior of the analytes are not well understood.

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Characterization of Tepoxalin and Its Related Compounds by High-Performance Liquid Chromatography/Mass Spectrometry

Cited by 8 publications

References 16 publications

Single and multiple‐dose pharmacokinetics of tepoxalin and its active metabolite after oral administration to rabbits (Oryctolagus cuniculus)

Single and multiple‐dose pharmacokinetics of tepoxalin and its active metabolite after oral administration to rabbits (Oryctolagus cuniculus)

Induction of VEGF by tepoxalin does not lead to increased tumour growth in a canine osteosarcoma xenograft

The use of liquid chromatography-mass spectrometry for the identification of drug degradation products in pharmaceutical formulations

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