Determination of aciclovir and ganciclovir in human plasma by liquid chromatography–spectrofluorimetric detection and stability studies in blood samples

Perrottet, Nancy; Béguin, Alexandre; Meylan, Pascal; Pascual, Manuel; Manuel, Oriol; Buclin, Thierry; Biollaz, J; Décosterd, Laurent A.

doi:10.1016/j.jchromb.2007.01.045

Cited by 43 publications

(42 citation statements)

References 21 publications

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“…2 The lower limit of detection was 0.1 mg/L, the inter-day coefficient of variation was ,3.5% and the range of inter-day deviations was comprised within 20.4% to 21.4%. Filtrate samples were analysed using calibration and quality controls prepared with blank filtrate.…”

Section: Sample Collection and Assaymentioning

confidence: 87%

Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients

Perrottet¹,

Robatel²,

Meylan³

et al. 2008

Journal of Antimicrobial Chemotherapy

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Objectives: To determine whether valganciclovir 450 mg every 48 h for cytomegalovirus (CMV) prophylaxis provides appropriate ganciclovir exposure in solid organ transplant recipients during continuous renal replacement therapy (CRRT).Patients and methods: Ganciclovir pharmacokinetics was intensively studied in two lung transplant recipients under valganciclovir 450 mg every 48 h over one dosing interval. In vitro experiments using blank whole blood spiked with ganciclovir further investigated exchanges between plasma and erythrocytes.Results: Ganciclovir disposition was characterized by apparent total body clearance of 3.3 and 5.8 L/h, terminal half-life of 16.9 and 14.1 h, and apparent volume of distribution of 60.3 and 104.9 L in Patients 1 and 2, respectively. The observed sieving coefficient was 1.05 and 0.96, and the haemofiltration clearance was 3.3 and 3.1 L/h. In vitro experiments confirmed rapid efflux of ganciclovir from red blood cells into plasma, increasing the apparent efficacy of haemofiltration.Conclusions: A valganciclovir dosage of 450 mg every 48 h appears adequate for patients under CRRT requiring prophylaxis for CMV infection, providing concentration levels in the range reported for 900 mg once daily dosing outside renal failure.

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Section: Sample Collection and Assaymentioning

confidence: 87%

Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients

Perrottet¹,

Robatel²,

Meylan³

et al. 2008

Journal of Antimicrobial Chemotherapy

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“…Quantification of azoles and caspofungin in whole blood stored at room temperature and at ϩ4°C was accurate for up to 24 h and 48 h, respectively. In contrast, blood samples containing anidulafungin needed to be processed immediately in order to avoid a significant increase in quantification, which may result from in vitro drug shifts into and from red blood cells (as previously observed for the antiviral agent ganciclovir [36,37]) and/or from a matrix effect associated with the hemolysis occurring during prolonged whole-blood storage. Quantification data for plasma stored at room temperature showed a significant decrease in voriconazole-NO during the first 24 h, of anidulafungin within 24 to 48 h, and of caspofungin within 48 to 72 h, whereas for all other azoles quantification remained accurate for up to 72 h. Quantification of the 8 analytes in plasmas stored at ϩ4C°and Ϫ80°C remained accurate for up to 72 h and 2 months, respectively.…”

Section: Discussionmentioning

confidence: 99%

Multiplex Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification in Human Plasma of Fluconazole, Itraconazole, Hydroxyitraconazole, Posaconazole, Voriconazole, Voriconazole- N -Oxide, Anidulafungin, and Caspofungin

Décosterd¹,

Rochat

Pesse

et al. 2010

Antimicrob Agents Chemother

117

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Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) method requiring 100 l of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (<9.2%), and analytical recovery (80.1 to 107%). The method is sensitive (lower limits of azole quantification, 0.01 to 0.1 g/ml; those of echinocandin quantification, 0.06 to 0.1 g/ml), accurate (intra-and interassay biases of ؊9.9 to ؉5% and ؊4.0 to ؉8.8%, respectively), and precise (intra-and interassay coefficients of variation of 1.2 to 11.1% and 1.2 to 8.9%, respectively) over clinical concentration ranges (upper limits of quantification, 5 to 50 g/ml). Thus, we developed a simple, rapid, and robust multiplex UPLC-MS/MS assay for simultaneous quantification of plasma concentrations of six antifungals and two metabolites. This offers, by optimized and cost-effective lab resource utilization, an efficient tool for daily routine TDM aimed at maximizing the real-time efficacy and safety of different recommended single-drug antifungal regimens and combination salvage therapies, as well as a tool for clinical research.Differences in oral drug bioavailability, altered volumes of distribution, drug-drug interactions, impaired hepatic and/or renal drug clearance, and the genetic background of hepatic metabolism contribute to the large intra-and interindividual variability of pharmacokinetics of antifungal agents in patients with life-threatening fungal infections. A given drug dosing regimen can yield very different plasma concentrations: subtherapeutic drug exposure may result in a lack of response to therapy and emergence of fungal resistance, while overexposure may increase the risk of toxicity (21,48,57,59). There is therefore increasing clinical evidence of the usefulness of therapeutic drug monitoring (TDM), which allows real-time adjustment of antifungal dosing aimed at optimizing the individual drug's pharmacokinetic/pharmacodynamic profile. This may be especially helpful for severely ill patients with multiple organ dysfunctions and comedi...

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“…The samples were sent without delay to the laboratory, and plasma was isolated by centrifugation and stored at Ϫ20°C to ensure stability up to the time of analysis. Plasma GCV levels were determined by reversed-phase high-performance liquid chromatography coupled with spectrofluorimetric detection according to a validated method (22). The calibration curve is linear between 0.1 and 10 mg/liter.…”

Section: Methodsmentioning

confidence: 99%

Population Pharmacokinetics of Ganciclovir in Solid-Organ Transplant Recipients Receiving Oral Valganciclovir

Perrottet

Csajka

Pascual

et al. 2009

Antimicrob Agents Chemother

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Determination of aciclovir and ganciclovir in human plasma by liquid chromatography–spectrofluorimetric detection and stability studies in blood samples

Cited by 43 publications

References 21 publications

Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients

Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients

Multiplex Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification in Human Plasma of Fluconazole, Itraconazole, Hydroxyitraconazole, Posaconazole, Voriconazole, Voriconazole- N -Oxide, Anidulafungin, and Caspofungin

Population Pharmacokinetics of Ganciclovir in Solid-Organ Transplant Recipients Receiving Oral Valganciclovir

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