Determination of a new antifungal agent, voriconazole, by multidimensional high-performance liquid chromatography with direct plasma injection onto a size-exclusion column

Stopher, D. A.; Gage, Richard

doi:10.1016/s0378-4347(96)00408-2

Cited by 73 publications

(68 citation statements)

References 22 publications

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“…Several reported the use of high performance liquid chromatography coupled with ultraviolet determination (HPLC-UV) [4,[13][14][15][16][17][18][19][20][21][22][23][24]. More recently, liquid chromatographic methods based on mass spectrometry (LC-MS/MS) detection have been developed to this purpose [25][26][27][28][29][30][31][32], although MS facilities are not always available in standard hospital laboratories, because they are expensive compared with a simple HPLC system.…”

Section: Patientsmentioning

confidence: 99%

A New HPLC Validated Method for Therapeutic Monitoring Of Triazoles in Human Plasma: First Results in Leukaemic Patients

Francia

Cardalana²,

P³

et al. 2015

Clin Exp Pharmacol

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Therapeutic drug monitoring of triazoles is widely used in clinical practice to optimize therapy, especially in those patients who need antifungal treatment as co-medications. Here it is described development and validation of a new chromatographic method in order to quantify voriconazole and posaconazole in human plasma by ultraviolet detection.After liquid extraction of analytes from plasma using acetonitrile, samples are evaporated to dryness and then reconstituted in mobile phase for chromatographic separation. Analysis is achieved on C18 reverse phase column and eluate is monitored at 250 nm. Mobile phase consisted of 35% water, 15% methanol, 50% acetonitrile. Flavone was used as internal standard; retention times (minutes) were, respectively, for voriconazole 3.9, posaconazole 7.9, flavone 7.1.Accuracy and variability were assayed by inter-and intra-day validation, conducted on three separate days. Methodology was used for the analysis of plasma samples of acute myeloid leukaemia patients in therapy with voriconazole or posaconazole for treatment of fungal infections, in order to perform therapeutic monitoring of antifungal drugs levels.Mean inter-and intra-day accuracy and variability were acceptable for both compounds; thus, method developed resulted linear in the range 0.125-8 µg/mL. Limits of quantification and limits of detection for voriconazole and posaconazole are, respectively, 0.100 and 0.050 µg/mL, and 0.030 and 0.020 µg/mL.It has been observed that voriconazole and posaconazole circulating levels achieved in patients are on average below the therapeutic range defined in literature.In conclusion, method developed and validated in order to quantify voriconazole and posaconazole in human plasma is accurate and precise; it is easily applicable and reproducible, and, therefore, it could be an useful tool in clinical routine to better manage patients in case of multi-therapy approach.

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Section: Patientsmentioning

confidence: 99%

A New HPLC Validated Method for Therapeutic Monitoring Of Triazoles in Human Plasma: First Results in Leukaemic Patients

Francia

Cardalana²,

P³

et al. 2015

Clin Exp Pharmacol

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“…[55][56][57][58][59][60][61][62][63][64][65][66][67][68] Most of these assays use high-performance liquid chromatography (HPLC) methods either with ultraviolet (UV) detection or coupled with mass spectrophotometry. [56][57][58][59][60][61][62][63][64][65][66][67][68] Other methods such as microbiological assays have also been investigated. 55,56 Some of the HPLC methods developed for quantifying voriconazole in plasma are limited by long turn-around time, complex procedures, and/or narrow quantification range that does not adequately reflect concentrations of voriconazole in the clinical setting.…”

Section: Drug Assaymentioning

confidence: 99%

“…55,56 Some of the HPLC methods developed for quantifying voriconazole in plasma are limited by long turn-around time, complex procedures, and/or narrow quantification range that does not adequately reflect concentrations of voriconazole in the clinical setting. 58,59,61,64,66,68 Although no therapeutic range has been decisively established, target concentrations reported in the literature have ranged from less than 0.5 to greater than 10 g/mL.…”

Section: Drug Assaymentioning

confidence: 99%

“…474 Two studies provided stability data, suggesting that plasma samples obtained for quantification of voriconazole are stable, with minimal change in concentration after 2 or 3 freeze-thaw cycles and storage at -25°C for up to 14 months. 60,64 Stability was also good (i.e., percent coefficient of variation [CV] less than 6.6%, accuracy 91.2%) when samples were stored at room temperature for 24 h in daylight or in the dark. 61 It appears that HPLC-UV may be the most acceptable analytic method for measuring voriconazole.…”

Section: Drug Assaymentioning

confidence: 99%

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Role of Therapeutic Drug Monitoring of Voriconazole in the Treatment of Invasive Fungal Infections

Kuo

Ensom

2009

CJHP

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Background: Voriconazole is a broad-spectrum, second-generation triazole antifungal agent with demonstrated efficacy in the treatment of invasive fungal infections caused by Aspergillus spp. and Candida spp. Given the characteristically poor prognosis of patients with invasive fungal infections and the protracted duration of treatment required, therapeutic monitoring of voriconazole is, in theory, an attractive method to optimize antifungal therapy. Objective:To determine the utility of therapeutic drug monitoring for voriconazole. Methods:A previously published decision-making algorithm was used to assess the currently available literature on therapeutic drug monitoring of voriconazole.Results: Several analytical methods can be used to quantify plasma or serum concentrations of voriconazole. Reasons for therapeutic monitoring of this drug include wide variability both within and between individuals secondary to drug properties, drug-drug interactions, and disease states. Furthermore, voriconazole follows nonlinear pharmacokinetics with saturable hepatic clearance. Another potential factor in favour of therapeutic drug monitoring for voriconazole is genetic polymorphism of CYP2C19, whereby patients who are homozygous for poor metabolism (about 19% of non-Indian Asians) can have 4-fold greater exposure to voriconazole. The concentrations of this drug are also greater in patients with hepatic impairment. Drug-drug interactions with other substrates of CYP2C9, CYP2C19, and CYP3A4 can also alter voriconazole concentrations. However, the correlations between plasma concentrations of voriconazole and its efficacy and toxicity are not well defined. Although lower and upper target thresholds of 0.25-2 mg/L and 4-6 mg/L, respectively, have been suggested, studies to date have not been appropriately designed or powered to reveal any definitive association. Conclusions:Routine therapeutic drug monitoring of voriconazole is not recommended except in certain circumstances, such as lack of response to therapy or evidence of toxicity, in which case selective monitoring of voriconazole concentrations may be of clinical utility. Méthodes : Un algorithme de prise de décision publié a été utilisé pour évaluer la documentation actuellement disponible sur le suivi thérapeutique pharmacologique du voriconazole. Résultats :Plusieurs méthodes analytiques peuvent servir à quantifier les concentrations sériques ou plasmatiques de voriconazole. Les raisons de recourir au suivi thérapeutique pharmacologique de ce médicament sont notamment la grande variabilité intra et interindividuelle attribuable aux propriétés du médicament, aux interactions médicament-médicament et aux affections. De plus, le voriconazole a un comportement pharmacocinétique non linéaire en raison d'une clairance hépatique saturable. Un autre facteur potentiellement en faveur du suivi thérapeutique pharmacologique du voriconazole est le polymorphisme génétique du CYP2C19 qui, chez les patients homozygotes ayant un faible métabolisme (environ 19 % des Asiatiques ...

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“…Studies concerning the safety, tolerability and pharmacokinetics of intravenous and/or oral dosing regimens of voriconazole demonstrated that voriconazole was generally safe and well tolerated, and it exhibited nonlinear pharmacokinetics. 9,10) Therapeutic monitoring of voriconazole in plasma, therefore, might be warranted in some patients who are at higher risk, especially due to PMs of the CYP2C19 genotype.Several methods including high-performance liquid chromatography (HPLC) combined with mass spectrometry, 11) or with UV detection, [12][13][14][15][16] and bioassay, 16) have been reported to determine voriconazole in biological fluids. The previously reported HPLC-UV methods are clinically useful, but sample pretreatment methods such as solid phase extraction 13) or a solvent extraction 15,16) followed by evaporation under nitrogen stream are required for the assay.…”

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confidence: 99%

Determination of the Antifungal Agent Voriconazole in Human Plasma Using a Simple Column-Switching High-Performance Liquid Chromatography and Its Application to a Pharmacokinetic Study

Nakagawa

Suzuki

Yamazaki

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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Voriconazole, (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol, is a widespectrum triazole antifungal agent (Fig. 1a). It selectively inhibits cytochrome P450 (CYP) dependent 14a-demethylase, which is a key enzyme in the fungal sterol biosynthesis pathway, specifically the conversion of lanosterol to ergosterol within the membrane component. Compared with other azole compounds, voriconazole shows a broader-spectrum antifungal activity, and it therefore can be used to treat severe or serious fungal infections, e.g., Candida spp., Aspergillus spp., Cryptococcus spp.2-4) Voriconazole is metabolized hepatically, primarily via the CYP isoenzymes CYP2C9, CYP2C19 and CYP 3A4. 4,5) The metabolites of voriconazole do not have antifungal activity. The CYP2C19 isozyme, which acts in the major metabolic pathway for voriconazole, exhibits significant genetic polymorphism, and consequently a number of poor metabolizers (PMs) are found. Potent interactions with voriconazole by CYP isozymes also affect the plasma levels of voriconazole. 5,6) The PMs are found with much higher frequency (18 to 23%) in the Japanese population than in North American and European white populations (3 to 5%). 7,8) Since the PMs result in increased plasma levels of voriconazole, 5,6) it is important to determine the concentration of voriconazole in human plasma to avoid side effects of voriconazole treatment, such as photopsia, skin rashes, liver dysfunction and so on. Studies concerning the safety, tolerability and pharmacokinetics of intravenous and/or oral dosing regimens of voriconazole demonstrated that voriconazole was generally safe and well tolerated, and it exhibited nonlinear pharmacokinetics. 9,10) Therapeutic monitoring of voriconazole in plasma, therefore, might be warranted in some patients who are at higher risk, especially due to PMs of the CYP2C19 genotype.Several methods including high-performance liquid chromatography (HPLC) combined with mass spectrometry, 11) or with UV detection, [12][13][14][15][16] and bioassay, 16) have been reported to determine voriconazole in biological fluids. The previously reported HPLC-UV methods are clinically useful, but sample pretreatment methods such as solid phase extraction 13) or a solvent extraction 15,16) followed by evaporation under nitrogen stream are required for the assay. Such tedious procedures are undesirable for many clinical applications, whereas an on-line HPLC method with direct plasma injection would be much more convenient. Therefore, there have been developed two methods; one is size exclusion chromatography coupled with a reversed-phase HPLC system with column-switching, 12) and another is a direct plasma injection HPLC micro method using an internal surface reversed-phase column. 14)In this paper, we describe a simple column-switching HPLC system with a direct plasma injection that does not involve any complicated pretreatment. We have used this system to study the pharmacokinetics of voriconazole in healthy volunteers following a sin...

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Determination of a new antifungal agent, voriconazole, by multidimensional high-performance liquid chromatography with direct plasma injection onto a size-exclusion column

Cited by 73 publications

References 22 publications

A New HPLC Validated Method for Therapeutic Monitoring Of Triazoles in Human Plasma: First Results in Leukaemic Patients

A New HPLC Validated Method for Therapeutic Monitoring Of Triazoles in Human Plasma: First Results in Leukaemic Patients

Role of Therapeutic Drug Monitoring of Voriconazole in the Treatment of Invasive Fungal Infections

Determination of the Antifungal Agent Voriconazole in Human Plasma Using a Simple Column-Switching High-Performance Liquid Chromatography and Its Application to a Pharmacokinetic Study

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