High-performance liquid chromatographic analysis of the anti-fungal agent SCH 56592 in dog serum

Kim, Hong; Likhari, Paul; Kumari, Pramila; Lin, Chin‐Chung; Nomeir, Amin A.

doi:10.1016/s0378-4347(99)00489-2

Cited by 13 publications

(9 citation statements)

References 9 publications

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“…This method is comparable with the method for the determination of posaconazole in dog serum described by Kim et al. using SCH 56984 as internal standard 12 . Unfortunately SCH 56984 was not available for us.…”

Section: Discussionmentioning

confidence: 52%

HPLC analysis of the antifungal agent posaconazole in patients with haematological diseases

Müller¹,

Arndt²,

Queckenberg³

et al. 2006

Mycoses

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Posaconazole is a new antifungal drug used in prophylaxis and therapy of fungal infections in patients with immunodeficiency. In the clinical development, posaconazole exhibits variable oral bioavailability. Hence drug monitoring is recommended. For this purpose, a rapid and a convenient high-performance liquid chromatography (HPLC) method has been developed. To 200 mul serum, 50 mul internal standard (itraconazole) was added. After precipitation of the proteins with acetonitrile, the clear supernatant was evaporated in a centrifugal evaporator, and the residue was dissolved in the HPLC elution. Separation was done on a chromatography performed by injecting a 50 mul aliquot of the resuspended sample onto a Multohyp C18 BDS column (250 x 4 mm). Column temperature was maintained at 50 degrees C. The flow rate was 1 ml min(-1). Retention time of posaconazole was about 9 min and those of itraconazole was 17 min. The limit of quantification was 50 mug l(-1) and the limit of detection about 10 mug l(-1). Until now the concentration of posaconazole was measured in 14 patients (64 samples). After a daily dosage of 600-800 mg posaconazole the serum concentrations varied between 100 and 3000 mug l(-1) (582 +/- 579 mug l(-1)). Oral bioavailability was especially low in patients with cytostatic therapy and/or bone marrow transplantation. Further studies are needed to establish the therapeutic range of the posaconazole concentrations.

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Section: Discussionmentioning

confidence: 52%

HPLC analysis of the antifungal agent posaconazole in patients with haematological diseases

Müller¹,

Arndt²,

Queckenberg³

et al. 2006

Mycoses

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“…The second step consists of the chromatographic separation performed on an RP18 analytical column followed by identification with a fluorescence detector. Several pre-existing methods for the determination of posaconazole in human serum report slightly lower LOD or LLOQ [17,27], but the sensitivity and selectivity of our method are absolutely sufficient for routine clinical use. Furthermore, as not every hospital or laboratory has access to mass spectrometry, methods based on fluorescence detection are likely to be a more suitable alternative for the standard routine.…”

Section: Resultsmentioning

confidence: 89%

“…Diazepam is used as internal standard in this method. The methods by Müller et al and Kim et al [17,27] involve the precipitation of serum proteins with acetonitrile or methanol, the first approach utilizing itraconazole as internal standard. Besides the possibility of interferences associated with sample pre-treatment, the use of internal standards is also related to analytical problems: not only the internal standard has to be absent in the patient sample, but also any other substance inducing a peak at the same retention time.…”

Section: Introductionmentioning

confidence: 99%

Determination of the antifungal agent posaconazole in human serum by HPLC with parallel column-switching technique

Neubauer

König

Bolek

et al. 2009

Journal of Chromatography B

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“…The pharmacokinetics of POC and ITC in plasma were investigated in three infected animals per each dosage group. Time points for minimal plasma sampling were determined on the basis of full plasma concentration profiles from the same species (5,22,33) with the aid of the Adapt II computer program (9). Plasma sampling was performed 6 days after inoculation.…”

Section: ϫ2mentioning

confidence: 99%

Antifungal Activity and Pharmacokinetics of Posaconazole (SCH 56592) in Treatment and Prevention of Experimental Invasive Pulmonary Aspergillosis: Correlation with Galactomannan Antigenemia

Petraitienė

Petraitis

Groll

et al. 2001

Antimicrob Agents Chemother

160

112

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The antifungal efficacy, safety, and pharmacokinetics of posaconazole (SCH 56592) (POC) were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits. Antifungal therapy consisted of POC at 2, 6, and 20 mg/kg of body weight per os; itraconazole (ITC) at 2, 6, and 20 mg/kg per os; or amphotericin B (AMB) at 1 mg/kg intravenously. Rabbits treated with POC showed a significant improvement in survival and significant reductions in pulmonary infarct scores, total lung weights, numbers of pulmonary CFU per gram, numbers of computerized-tomography-monitored pulmonary lesions, and levels of galactomannan antigenemia. AMB and POC had comparable therapeutic efficacies by all parameters. By comparison, animals treated with ITC had no significant changes in outcome variables in comparison to those of untreated controls (UC). Rabbits receiving prophylactic POC at all dosages showed a significant reduction in infarct scores, total lung weights, and organism clearance from lung tissue in comparison to results for UC (P < 0.01). There was dosage-dependent microbiological clearance of A. fumigatus from lung tissue in response to POC. Serum creatinine levels were greater (P < 0.01) in AMB-treated animals than in UC and POC-or ITC-treated rabbits. There was no elevation of serum hepatic transaminase levels in POC-or ITC-treated rabbits. The pharmacokinetics of POC and ITC in plasma demonstrated dose dependency after multiple dosing. The 2-, 6-, and 20-mg/kg dosages of POC maintained plasma drug levels above the MICs for the entire 24-h dosing interval. In summary, POC at >6 mg/kg/day per os generated sustained concentrations in plasma of >1 g/ml that were as effective in the treatment and prevention of invasive pulmonary aspergillosis as AMB at 1 mg/kg/day and more effective than cyclodextrin ITC at >6 mg/kg/day per os in persistently neutropenic rabbits.

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High-performance liquid chromatographic analysis of the anti-fungal agent SCH 56592 in dog serum

Cited by 13 publications

References 9 publications

HPLC analysis of the antifungal agent posaconazole in patients with haematological diseases

HPLC analysis of the antifungal agent posaconazole in patients with haematological diseases

Determination of the antifungal agent posaconazole in human serum by HPLC with parallel column-switching technique

Antifungal Activity and Pharmacokinetics of Posaconazole (SCH 56592) in Treatment and Prevention of Experimental Invasive Pulmonary Aspergillosis: Correlation with Galactomannan Antigenemia

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