Optimization and validation of a high-performance liquid chromatographic method with UV detection for the determination of ketoconazole in canine plasma

Vertzoni, Maria; Archontaki, Helen

doi:10.1016/j.jchromb.2006.03.010

Cited by 29 publications

(20 citation statements)

References 20 publications

(42 reference statements)

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“…Using HPLC the non-stereospecific LLQ of KTZ ranged from 62.5 ng/mL using fluorescence detection, to 100 ng/mL using UV detection, based on 100 μL of human plasma (Alton, 1980;Yuen and Peh, 1998). In canine plasma, a LLQ of 15 ng/mL was reported using HPLC and UV detection based on 100 μL plasma (Vertzoni et al, 2006). In rat plasma the LLQ ranged from 2 ng/mL using LC/MS to more than 200 ng/mL using UV detection based on 100 μL and 1 mL plasma, respectively (Riley and James, 1986;Huang et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

A stereospecific high‐performance liquid chromatographic assay for the determination of ketoconazole enantiomers in rat plasma

Hamdy

Brocks

2008

Biomedical Chromatography

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A stereospecific high-performance liquid chromatographic assay was developed for the quantitation of ketoconazole enantiomers (KTZ) in rat plasma. After protein precipitation of 100 microL plasma using acetonitrile, a wash step was performed using hexane. The supernatant was removed and KTZ enantiomers and amiodarone, the internal standard, were extracted using liquid-liquid extraction with tert-butyl methyl ether. After transfer and evaporation of the organic layer, the residue was reconstituted in mobile phase and injected into the HPLC through a chiral column. The mobile phase consisted of hexane:ethanol:2-propanol with diethyl amine, pumped at 1.5 mL/min. All components eluted within 18 min. KTZ enantiomers were baseline resolved and peaks were symmetrical in appearance with no interferences. Calibration curves were linear over the range 62.5-5000 ng/mL of enantiomer. The intraday and interday CV% assessments were

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Section: Discussionmentioning

confidence: 99%

A stereospecific high‐performance liquid chromatographic assay for the determination of ketoconazole enantiomers in rat plasma

Hamdy

Brocks

2008

Biomedical Chromatography

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“…This analysis was performed at Uppsala University in accordance with a previously published method (Vertzoni et al, 2006). The samples were prepared by the addition of internal standard (5 g/ml 9-acetlyanthracene) and acetonitrile (100 l of plasma-40 l of internal standard-60 l of acetonitrile), followed by centrifugation.…”

Section: Methodsmentioning

confidence: 99%

Effects of Ketoconazole on the In Vivo Biotransformation and Hepatobiliary Transport of the Thrombin Inhibitor AZD0837 in Pigs

Matsson¹,

Palm²,

Eriksson³

et al. 2010

Drug Metab Dispos

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To investigate the biotransformation of AZD0837 and the effect of ketoconazole on this process, we used an experimental model in pigs that allows repeated sampling from three blood vessels, the bile duct, and a perfused intestinal segment. The pigs received AZD0837 (500 mg) given enterally either alone (n ‫؍‬ 5) or together with single-dose ketoconazole (600 mg) (n ‫؍‬ 6). The prodrug (n ‫؍‬ 2) and its active metabolite (n ‫؍‬ 2) were also administered intravenously to provide reference doses. The plasma data revealed considerable interindividual variation in the exposure of the prodrug, intermediate metabolite, and active metabolite. However, AR-H067637 was detected at very high concentrations in the bile with low variability (Ae bile ‫؍‬ 53 ؎ 6% of the enteral dose), showing that the compound had indeed been formed in all of the animals and efficiently transported into the bile canaliculi. Concomitant dosing with ketoconazole increased the area under the plasma concentration-time curve for AZD0837 (by 99%) and for AR-H067637 (by 51%). The effect on the prodrug most likely arose from inhibited CYP3A-mediated metabolism. Reduced metabolism also seemed to explain the increased plasma exposure of the active compound because ketoconazole prolonged the terminal half-life with no apparent effect on the extensive biliary excretion and biliary clearance. These in vivo results were supported by in vitro depletion experiments for AR-H067637 in pig liver microsomes with and without the addition of ketoconazole.

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“…The collected cell pellets were ruptured by subjecting to two repeated cycles of freezing and thawing, followed by ultrasonication for 10 min. Cell lysates were centrifuged using Laboratory Centrifuge 3K30 at 15,000 rpm for 1 h at 4°C, and the concentration of the drug in the supernatant was determined using highperformance liquid chromatography (HPLC) method previously reported, 20 except for slight modifications. An isocratic HPLC method using C18 analytical column (4×250 mm, 5 µm; Thermo Fischer Scientific) was performed.…”

Section: Transcorneal Permeationmentioning

confidence: 99%

A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole

Ahmed

Aljaeid²

2017

IJN

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Oral ketoconazole therapy is commonly associated with serious hepatotoxicity. Improving ocular drug delivery could be sufficient to treat eye fungal infections. The purpose of this study was to develop optimized ketoconazole poly(lactide-co-glycolide) nanoparticles (NPs) with subsequent loading into in situ gel (ISG) formulation for ophthalmic drug delivery. Three formulation factors were optimized for their effect on particle size (Y1) and entrapment efficiency (Y2) utilizing central composite experimental design. Interaction among components was studied using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. Ketoconazole crystalline state was studied using X-ray powder diffraction. Six different polymeric ISG formulations were prepared and loaded with either optimized NPs or a pure drug. The prepared ISG formulations were characterized for in vitro gelation, drug release and antifungal activity. The permeation through human epithelial cell line was also investigated. The results revealed that all the studied formulation parameters significantly affected Y1 and Y2 of the developed NPs. DSC and FTIR studies illustrated compatibility among NP components, while there was a change from the crystalline state to the amorphous state of the NPs. The in vitro release from the ISG formulations loaded with drug NPs showed sustained and enhanced drug release compared to pure drug formulations. In addition, ISG loaded with NPs showed enhanced anti-fungal activity compared to pure drug formulations. Alginate–chitosan ISG formulation loaded with optimized ketoconazole NPs illustrated higher drug permeation through epithelial cell lines and is considered as an effective ophthalmic drug delivery in the treatment of fungal eye infections.

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Optimization and validation of a high-performance liquid chromatographic method with UV detection for the determination of ketoconazole in canine plasma

Cited by 29 publications

References 20 publications

A stereospecific high‐performance liquid chromatographic assay for the determination of ketoconazole enantiomers in rat plasma

A stereospecific high‐performance liquid chromatographic assay for the determination of ketoconazole enantiomers in rat plasma

Effects of Ketoconazole on the In Vivo Biotransformation and Hepatobiliary Transport of the Thrombin Inhibitor AZD0837 in Pigs

A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole

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