A Rapid High-Performance LC-MS/MS Method for Therapeutic Drug Monitoring of Voriconazole, Posaconazole, Fluconazole, and Itraconazole in Human Serum

Xiao, Yingying; Xu, Yan-Kang; Pattengale, Paul K.; O’Gorman, Maurice R.G.; Fu, Xiaowei

doi:10.1373/jalm.2016.022756

Cited by 15 publications

(8 citation statements)

References 20 publications

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“…Recently, other procedures have been reported for the simultaneous determination of antifungals, as shown in Table 5. Yi et al, reported a method for detecting six compounds including fluconazole, isavuconazole, itraconazole, hydroxy-itraconazole, posaconazole, and voriconazole [30]. Smith et al, proposed a method specifically for detecting voriconazole, isavuconazole, and posaconazole [31].…”

Section: Comparison With Reported Methodsmentioning

confidence: 99%

Simultaneous Quantification of Seven Antifungal Agents in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry

Li,

Cai

et al. 2023

Pharmaceuticals

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Systemic antifungal agents are essential for high-risk patients undergoing immunosuppressive therapy or cancer chemotherapy because of the rapid increase in opportunistic fungal infections. Therapeutic drug monitoring is crucial to ensuring the efficacy and safety of antifungal agents owing to their pharmacokinetic variability. In the present study, we developed and validated a quantitative method for the simultaneous detection of seven commonly used antifungal drugs (amphotericin B, isavuconazole, voriconazole, fluconazole, posaconazole, caspofungin, and micafungin) using liquid chromatography-tandem mass spectrometry. Methanol (containing 0.1% formic acid) was used for protein precipitation and only 50 μL of serum was required for the analysis. Chromatographic separation was conducted using a Waters Acquity UPLC C8 column, and one stable isotope-labeled agent and two analogs were used as internal standards. The calibration curves ranged from 0.1 to 50 μg/mL for all agents, and the correlation coefficient (R2) for all calibration curves was above 0.9835. The intra-day precision (1.2–11.2%), inter-day precision (2.4–13.2%), and mean bias values (−10.9 to 13.6%) were within an acceptable range of ±15%. Successful implementation of the developed method in clinical practice would facilitate the effective monitoring of these antifungal agents.

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Section: Comparison With Reported Methodsmentioning

confidence: 99%

Simultaneous Quantification of Seven Antifungal Agents in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry

Li,

Cai

et al. 2023

Pharmaceuticals

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“…The main preparation of posaconazole blood samples were protein precipitation, liquid–liquid extraction and solid‐phase extraction. Among the methods summarized in Table 1, twenty‐eight studies used protein precipitation, with acetonitrile selected as the precipitant in most of them 24,27,31–33,39,42–49,51–58,60,61,63–66 . Eight studies used liquid–liquid extraction, with dichloromethane and n‐hexane as the main extractants, 25,29,30,35,36,40,41,59 and solid phase extraction was used in five studies 26,28,34,62 .…”

Section: What Is Known and Objectivementioning

confidence: 99%

“…Thirteen studies used LC-MS/MS. [42][43][44][45][46][47][48][49][50][51][52][53][54] Four studies used HPLC-MS/MS, [56][57][58][59] and seven studies used UHPLC-MS/MS. [60][61][62][63][64][65][66] In addition, Reddy et al, 42 van der Elst et al 46 and Baietto et al 59 described the method to determine the concentration of posaconazole in dried blood spot (DBS) samples.…”

Section: What Is Known and Objectivementioning

confidence: 99%

“…Among the methods summarized in Table 1, twenty-eight studies used protein precipitation, with acetonitrile selected as the precipitant in most of them. 24,27,[31][32][33]39,[42][43][44][45][46][47][48][49][51][52][53][54][55][56][57][58]60,61,[63][64][65][66] Eight studies used liquid-liquid extraction, with dichloromethane and n-hexane as the main extractants, 25,29,30,35,36,40,41,59 and solid phase extraction was used in five studies. 26,28,34,62 Most liquid chromatographic methods select acetonitrile as the organic phase and water or phosphate buffer as the aqueous phase, with a linear range from a minimum concentration of 0.05 mg/L to a maximum concentration of 16 mg/L.…”

Section: What Is Known and Objectivementioning

confidence: 99%

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Progress of triazole antifungal agent posaconazole in individualized therapy

Shu

Shi

Yang

et al. 2022

Clinical Pharmacy Therapeu

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What is known and objective: Posaconazole is the second-generation triazole antifungal agent with widespread clinical application. Posaconazole exposure is influenced by various factors such as drug interactions, disease state and diet, resulting in a high interindividual variability in many patients and failure to ensure therapeutic efficacy. Therefore, it is necessary to conduct individualized therapy on posaconazole to ensure the efficacy and safety of treatment.Methods: Articles were identified through PubMed using the keywords such as "posaconazole," "therapeutic drug monitoring" and "Population pharmacokinetics" from 1 January 2001 to 30 April 2022. Results and discussion: In this paper, we review the individualized treatment studies of posaconazole from the three aspects of therapeutic drug monitoring, population pharmacokinetic study and Monte Carlo simulation to provide reference for in-depth individualized posaconazole dosing studies. What is new and conclusion: This review suggests that therapeutic drug monitoring should be performed in patients taking posaconazole to adjust the dosage and assess the efficacy and cost-effectiveness of posaconazole under different clinical conditions and different dosing regimens through Monte Carlo simulations. In the future, a more detailed delineation and comprehensive examination of posaconazole PPK for specific populations requires further study.

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“…Although the pharmacokinetics of fluconazole after fosfluconazole treatment in adults is well documented, an appropriate, validated dosing regimen for neonates with VLBW and ELBW does not yet exist, and further clinical pharmacokinetic (PK) research is required. However, to be able detect fluconazole at a quantification limit of 0.5 μg/mL for PK studies [8], a 100 to 200 μL whole blood sample (about 50 to 100 μL of plasma or serum) is required for a single assay (Table 1) [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. To perform replicate analysis to reduce the preparation bias, two-to threefold this quantity is needed [25].…”

Section: Introductionmentioning

confidence: 99%

A sensitive method for analyzing fluconazole in extremely small volumes of neonatal serum

Saito

Tanzawa

Kojo

et al. 2020

J Pharm Health Care Sci

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Background: The need for a large volume of serum sample significantly reduces the feasibility of neonatal pharmacokinetic studies in daily practice, which must often rely on scavenged or opportunistic sampling. This problem is most apparent in preterm newborns, where ethical and practical considerations prohibit the collection of large sample volumes. Most of the fluconazole analysis assays published thus far required a minimum serum sample of 50 to 100 μL for a single assay. The purpose of the present study was to develop and validate a sensitive method requiring a smaller sample volume (10 μL) to satisfy clinically relevant research requirements. Methods: Following simple protein precipitation and centrifugation, the filtrated supernatant was injected into a liquid chromatography system and separated with a C18 reverse-phase column. Fluconazole and the internal standard (IS, fluconazole-d4) were detected and quantified using tandem mass spectrometry. The method was validated with reference to the Food and Drug Administration's Guidance for Industry. Accuracy and precision were evaluated at six quality control concentration levels (ranging from 0.01 to 100 μg/mL). Results: Investigated calibration curves were linear in the 0.01-100 μg/mL range. Intra-and inter-day accuracy (− 7.7 to 7.4%) and precision (0.3 to 6.0%) were below 15%. The calculated limit of detection and the lower limit of quantification (LLOQ) was 0.0019 μg/mL and 0.0031 μg/mL, respectively. Fluconazole in the prepared samples was stable for at least 4 months at − 20°C and − 80°C. This method was applied to analyze 234 serum samples from ten neonates who received fosfluconazole, a water-soluble phosphate prodrug of fluconazole which converts to fluconazole in the body, as part of a pharmacokinetic study using daily scavenged laboratory samples. The median (range) concentration up to 72 h after fosfluconazole administration was 2.9 (0.02 to 26.8 μg/mL) μg/mL, which was within the range of the calibration curve. Conclusion: Fluconazole was able to be detected in an extremely small volume (10 μL) of serum from neonates receiving fosfluconazole. The method presented here can be used to quantify fluconazole concentrations for pharmacokinetic studies of the neonatal population by using scavenged samples.

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A Rapid High-Performance LC-MS/MS Method for Therapeutic Drug Monitoring of Voriconazole, Posaconazole, Fluconazole, and Itraconazole in Human Serum

Cited by 15 publications

References 20 publications

Simultaneous Quantification of Seven Antifungal Agents in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry

Simultaneous Quantification of Seven Antifungal Agents in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry

Progress of triazole antifungal agent posaconazole in individualized therapy

A sensitive method for analyzing fluconazole in extremely small volumes of neonatal serum

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