Quantification of dapaconazole in human plasma using high-performance liquid chromatography coupled to tandem mass spectrometry: Application to a phase I study

Moraes, Fernanda Custódio de; Bittencourt, Samara Favi; Perissutti, Elisa; Frencentese, Francesco; Arruda, André Moreira Martins; Chen, Lu Shi; Babadópulos, Tainah; Nucci, Gilberto De

doi:10.1016/j.jchromb.2014.01.053

Cited by 6 publications

(3 citation statements)

References 10 publications

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“…About 1.7 million deaths occur due to these infections each year [1]. Azole antifungals are the most commonly used drug molecules in therapeutic applications [2]. These are synthetic compounds and generally classified as imidazoles or triazoles which include two or three nitrogen atoms, respectively, in the fivemembered ring systems.…”

Section: Introductionmentioning

confidence: 99%

A Study on the Retention Behavior of Some Imidazole Antimycotic Drugs in Acetonitrile-Water Binary Mixtures

SEÇİLMİŞ

Demıralay

Poturcu

2022

Ankara Universitesi Eczacilik Fakultesi Dergisi

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Objective: In this study, the thermodynamic protonation constant ( 𝑝𝐾 𝑎 𝑠 𝑠) of antifungal azole derivative miconazole and tioconazole were investigated by the reversed-phase liquid chromatography (RPLC) method. Although classical stationary phases are the most commonly used column-packed materials in the analyses of these compounds by the RPLC method, the determination of the pKa value of miconazole and tioconazole with a cyano-based column has not been reported so far.Material and Method: Chromatographic behavior of the selected compounds was determined with Ultra Cyano column (Restek ® , 150×3.0 mm I.D, 3µm) which is compatible with hydrophobic compounds. The dependence of the retention times on the acetonitrile content of the mobile phase and the effect of the mobile phase pH on the chromatographic retention was determined for each compound by changing the pH in the range of 3.0-7.50. Result and Discussion: The 𝑝𝐾 𝑎 𝑠 𝑠 values were determined by a nonlinear regression program. The thermodynamic aqueous pKa ( 𝑝𝐾 𝑎 𝑤 𝑤 ) value of the studied compounds was calculated from the 𝑝𝐾 𝑎 𝑠 𝑠 value by using the macroscopic parameters (dielectric constant and mole fraction) that play an important role in the solvent properties. The calculated 𝑝𝐾 𝑎 𝑤 𝑤 values were compared with literature values.

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Section: Introductionmentioning

confidence: 99%

A Study on the Retention Behavior of Some Imidazole Antimycotic Drugs in Acetonitrile-Water Binary Mixtures

SEÇİLMİŞ

Demıralay

Poturcu

2022

Ankara Universitesi Eczacilik Fakultesi Dergisi

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“…Dapaconazole, a novel imidazole, has shown antifungal activity against several pathogenic fungi, such as Tricophyton verrucosum , Tricophyton rubrum , Trycophyton mantagrophutes , Microsporum gypseum , Microsporum canis , and Aspergillus niger [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Dapaconazole demonstrated noninferior efficacy to miconazole for the topical treatment of tinea cruris [ 4 ], to ketoconazole for treating interdigital tinea pedis [ 3 ], and pityriasis versicolor [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Prospective Prediction of Dapaconazole Clinical Drug–Drug Interactions Using an In Vitro to In Vivo Extrapolation Equation and PBPK Modeling

et al. 2022

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This study predicted dapaconazole clinical drug–drug interactions (DDIs) over the main Cytochrome P450 (CYP) isoenzymes using static (in vitro to in vivo extrapolation equation, IVIVE) and dynamic (PBPK model) approaches. The in vitro inhibition of main CYP450 isoenzymes by dapaconazole in a human liver microsome incubation medium was evaluated. A dapaconazole PBPK model (Simcyp version 20) in dogs was developed and qualified using observed data and was scaled up for humans. Static and dynamic models to predict DDIs following current FDA guidelines were applied. The in vitro dapaconazole inhibition was observed for all isoforms investigated, including CYP1A2 (IC50 of 3.68 µM), CYP2A6 (20.7 µM), 2C8 (104.1 µM), 2C9 (0.22 µM), 2C19 (0.05 µM), 2D6 (0.87 µM), and 3A4 (0.008–0.03 µM). The dynamic (PBPK) and static DDI mechanistic model-based analyses suggest that dapaconazole is a weak inhibitor (AUCR > 1.25 and <2) of CYP1A2 and CYP2C9, a moderate inhibitor (AUCR > 2 and <5) of CYP2C8 and CYP2D6, and a strong inhibitor (AUCR ≥ 5) of CYP2C19 and CYP3A, considering a clinical scenario. The results presented may be a useful guide for future in vivo and clinical dapaconazole studies.

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“…In order to accurately detect the intracellular concentration, high performance liquid chromatography with tandem mass spectrometry (HPLC–MS/MS) was used to measure the intracellular FLC levels in C. albicans . At present, several fast HPLC–MS/MS methods have been validated and reported for monitoring the antifungal drug concentration in plasma or other body liquid, including FLC, itraconazole, and other antifungal agents ( Van De Steene and Lambert, 2008 ; Tang et al, 2010 ; Zhang et al, 2011 ; Alebic-Kolbah and Modesitt, 2012 ; Beste et al, 2012 ; Zgoła-Grześkowiak and Grześkowiak, 2013 ; de Moraes et al, 2014 ; Wadsworth et al, 2017 ; Różalska et al, 2018 ; Xiang et al, 2018 ). Actually, quantitative analysis of FLC in C. albicans via HPLC-MS/MS has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a sensitive LC-MS/MS method for determination of intracellular concentration of fluconazole in Candida albicans

Wang

Wang²,

Cai³

et al. 2022

Front. Microbiol.

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Systemic candidiasis is the fourth leading cause of healthcare-associated infections worldwide. The combination therapy based on existing antifungal agents is well-established to overcome drug resistance and restore antifungal efficacy against drug-resistant strains. In this study, a simple and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed to quantify the intracellular fluconazole (FLC) content in the opportunistic human fungal pathogen Candida albicans. The cell lysates were prepared by lysing C. albicans cells with Precellys homogenizers and FLC was extracted with methylene chloride. The entire extraction approach was simple, precise and reliable. The extracts were separated on a Zorbax SB-C18 column using a mobile phase of acetonitrile (solvent A) and deionized water plus 0.1% formic acid. FLC and ketoconazole (KCZ, internal standard) were monitored in positive mode using electrospray ionization source. The multiple reaction monitoring transitions (precursor to product) were monitored for FLC m/z 307.1 → 238.2 and for the internal standard KCZ m/z 531.2 → 489.1. The linear for this method were in the range from 5.0 to 1000.0 ng/mL. The precision and accuracy of the samples were relative standard deviations (RSD) < 1.0% for intra-day and RSD < 0.51% for inter-day. The overall recovery of FLC from samples was higher than 77.61%. Furthermore, this method was successfully applied and validated in 36 clinical isolated strains. Taken together, we established a highly accurate, efficient, and reproducible method for quantifying the intracellular content of FLC in C. albicans.

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Quantification of dapaconazole in human plasma using high-performance liquid chromatography coupled to tandem mass spectrometry: Application to a phase I study

Cited by 6 publications

References 10 publications

A Study on the Retention Behavior of Some Imidazole Antimycotic Drugs in Acetonitrile-Water Binary Mixtures

A Study on the Retention Behavior of Some Imidazole Antimycotic Drugs in Acetonitrile-Water Binary Mixtures

Prospective Prediction of Dapaconazole Clinical Drug–Drug Interactions Using an In Vitro to In Vivo Extrapolation Equation and PBPK Modeling

Development and validation of a sensitive LC-MS/MS method for determination of intracellular concentration of fluconazole in Candida albicans

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