Validation of rapid and simple LC–MS/MS method for determination of voriconazole in rat plasma

Araújo, Bibiana Verlindo de; Conrado, Daniela J.; Palma, Eduardo C.; Costa, Teresa Dalla

doi:10.1016/j.jpba.2007.03.026

Cited by 33 publications

(24 citation statements)

References 19 publications

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“…The plasma samples were quantified by LC-MS/MS for determination of VRC in rat plasma, using ketoconazole as the internal standard (IS) (38). The retention times of VRC and the IS were approximately 3.3 and 2.7 min, respectively.…”

Section: Microorganismsmentioning

confidence: 99%

Influence of Experimental Cryptococcal Meningitis in Wistar Rats on Voriconazole Brain Penetration Assessed by Microdialysis

Alves

Staudt

Silva

et al. 2017

Antimicrob Agents Chemother

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To make advances in the treatment of cryptococcal meningitis, it is crucial to know a given drug's free fraction that reaches the biophase. In the present study, we applied microdialysis (D) as a tool to determine the free levels reached by voriconazole (VRC) in the brains of healthy and Cryptococcus neoformans-infected rats. The infection was induced by the intravenous (i.v.) administration of 1 ϫ 10 5 CFU of yeast. The dose administered was 5 mg/kg (of body weight) of VRC, given i.v. Plasma and microdialysate samples were analyzed by liquid chromatographytandem mass spectrometry (LC-MS/MS) and LC-UV methods. The free brain/free plasma ratio (fT) and population pharmacokinetic (popPK) analyses were performed to evaluate the impact of infection on PK parameters of the drug. The brain penetration ratio showed an increase on brain exposure in infected animals (fT healthy ϭ 0.85 versus fT infected ϭ 1.86). The structural PK model with two compartments and Michaelis-Menten (MM) elimination describes the VRC concentration-time profile in plasma and tissue simultaneously. The covariate infection was included in volume of distribution in the peripheral compartment in healthy animals (V 2 ) and maximum rate of metabolism (V M ). The levels reached in infected tissues were higher than the values described for MIC of VRC for Cryptococccus neoformans (0.03 to 0.5 g ml Ϫ1 ), indicating its great potential to treat meningitis associated with C. neoformans.

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Section: Microorganismsmentioning

confidence: 99%

Influence of Experimental Cryptococcal Meningitis in Wistar Rats on Voriconazole Brain Penetration Assessed by Microdialysis

Alves

Staudt

Silva

et al. 2017

Antimicrob Agents Chemother

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“…Analytical methods using liquid chromatography coupled with triple-quadrupole mass spectrometry (LC-MS/MS) have been reported for the quantification of single antifungals in biological fluids, including fluconazole (FLC) (14,34,49), itraconazole (ITZ) (39,62) and its active metabolite (hydroxyitraconazole [OH-ITZ]) (4,6,27,53), voriconazole (VRC) (2,15,26,54,63), posaconazole (PSC) (10, 40a, 44, 52), caspofungin (CASPO) (7,16,40), and anidulafungin (ANI) (13). LC-MS/MS assays were recently reported for the simultaneous quantification of posaconazole, voriconazole, isavuconazole, caspofungin, anidulafungin, and micafungin in different peripheral blood compartments (19) and of itraconazole, voriconazole, and posaconazole in blood (3).…”

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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

112

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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 quantification of voriconazole in biological fluids by HPLC [7][8][9][10][11][12] and by LC-MS [13][14][15][16][17][18][19][20] methods has been reported. Because voriconazole determination to monitor therapeutic regiments is not yet established, often only a few samples have to be measured in a single run.…”

Section: Abstract: Voriconazole; Liquid Chromatography Coupled With mentioning

confidence: 99%

“…On the other hand, clinicians often require results on the same day, which makes the turnaround time for drug analysis critical, especially if other drugs have to be measured with the same equipment. Recently, several different methods have been described using LC-MS or LC-MS/MS techniques for the determination of voriconazole in the aqueous humor, 13) serum, 14,15) and plasma, 16,17) or simultaneously quantitate concentrations of different antifungal drugs including voriconazole in human plasma 18,19) or serum. 20) However, the analysis times were found be 4 to 13 min for these methods.…”

Section: Abstract: Voriconazole; Liquid Chromatography Coupled With mentioning

confidence: 99%

Fast and Reliable Determination of Voriconazole in Human Plasma by LC-APCI-MS/MS

Xiong

Duan

Zhai

et al. 2010

Bioscience, Biotechnology, and Biochemistry

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Validation of rapid and simple LC–MS/MS method for determination of voriconazole in rat plasma

Cited by 33 publications

References 19 publications

Influence of Experimental Cryptococcal Meningitis in Wistar Rats on Voriconazole Brain Penetration Assessed by Microdialysis

Influence of Experimental Cryptococcal Meningitis in Wistar Rats on Voriconazole Brain Penetration Assessed by Microdialysis

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

Fast and Reliable Determination of Voriconazole in Human Plasma by LC-APCI-MS/MS

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