Determination of posaconazole concentration with LC–MS/MS in adult patients with hematologic malignancy

Chae, Hyojin; Cho, Sung‐Yeon; Yu, Haein; Cha, Kyoungho; Lee, Seongok; Kim, Myungshin; Kim, Yonggoo; Kim, Yoo-Jin; Kim, Hee-Je; Lee, Dong Gun

doi:10.1016/j.cca.2015.08.023

Cited by 16 publications

(30 citation statements)

References 31 publications

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“…The technique has been proved to be the most rapid and simplest procedure for sample preparation, and is widely accepted in many clinical and analytical laboratories. Quantitative extraction of posaconazole from human plasma or serum has been reported previously by using acetonitrile [22,26,29,31], methanol [23,31,33] or mixtures of both solvents [19][20][21]25] as the extracting reagent in sample preparation. The use of perchloric acid as a precipitating agent had also been previously examined by Zhang et al [31], and the addition of perchloric acid to methanol extraction proved to be advantageous.…”

Section: Solvent Extraction In a Single Dilution Stepmentioning

confidence: 99%

“…Therapeutic drug monitoring of a patient's serum or plasma has been a useful tool to detect drug exposures outside of the therapeutic window and to help individualize a dosage regimen and treatment, increasing therapeutic efficacy, and decreasing side effects . Reported methods for the analysis of posaconazole are mostly high-performance liquid chromatography (HPLC) with mass spectrometry [13][14][15][16][17][18][19][20][21][22][23][24][25], ultraviolet [26][27][28][29][30][31] and fluorescence [32][33][34][35] detections. Mass spectrometry (MS) and tandem mass spectrometry (MS/MS) are superior in sensitivity and specificity to ultraviolet (UV) and fluorescence (FL) detections.…”

Section: Introductionmentioning

confidence: 99%

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Determination of Posaconazole in Plasma/Serum by High-Performance Liquid Chromatography with Fluorescence Detection

Tang

2017

Separations

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Abstract:A sensitive high-performance liquid chromatographic (HPLC) method is described for the determination of posaconazole in human plasma/serum. The method is based on a single dilution step by treating the sample with methanol, and followed by the direct injection of the sample into the HPLC system. Posaconazole and internal standard ketoconazole in the methanol extract are subsequently analyzed by using a fluorescence (FL) detector at optimized wavelengths (excitation 245 nm and emission 380 nm). The method achieves a linear detector response for peak height measurements over the concentration range of 0.1-10 µg/mL which adequately covers the therapeutic range for appropriate patient monitoring. The chromatographic time is less than 8 min per injection, an improvement over most published HPLC/FL or HPLC/UV methods. The method's limit of quantitation, linearity, imprecision, and accuracy met all criteria required by the Guidance for Industry Bioanalytical Method Validation. In comparison to other published methods, the current method would be of interest to analytical and clinical laboratories because it employs simple, rapid, and cost-effective procedures.

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Section: Solvent Extraction In a Single Dilution Stepmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Determination of Posaconazole in Plasma/Serum by High-Performance Liquid Chromatography with Fluorescence Detection

Tang

2017

Separations

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“…For seven years, posaconazole was only available as an oral suspension. However, this formulation has unpredictable bioavailability that is affected by many variables, including meals and acid suppression therapy [34], potentially leading to sub-therapeutic plasma concentrations and breakthrough fungal infections [567]. To improve bioavailability, a posaconazole tablet formulation was developed, and was approved in 2013 [89].…”

mentioning

confidence: 99%

“…PPC was measured by liquid chromatography-tandem mass spectrometry on Day 3, Day 8, and Day 15 [4]. We considered a PPC of ≥700 ng/mL to be optimal for antifungal prophylaxis, based on Food and Drug Administration ( FDA) pharmacokinetic data that shows a higher incidence of breakthrough invasive fungal infections in patients with a C avg of <700 ng/mL [121314].…”

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confidence: 99%

Comparison of Plasma Concentrations of Posaconazole with the Oral Suspension and Tablet in Korean Patients with Hematologic Malignancies

et al. 2017

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The posaconazole tablet formulation was developed to have improved bioavailability compared to the oral suspension. Here, we compared posaconazole plasma concentration (PPC) with the posaconazole oral suspension versus the tablet in Korean patients undergoing remission induction chemotherapy for hematologic malignancies. PPC was measured at 3, 8, and 15 days of treatment with the oral suspension (174 patients) or the tablet (40 patients). At all time-points, mean PPC was significantly higher with the tablet compared to the oral suspension. Our findings suggest that posaconazole tablets generate an optimal PPC earlier and in more patients than the oral suspension among Korean patients.

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“…Until recently, PCZ was only available as an oral suspension (OS) formulation. The OS formulation of PCZ exhibits highly variable inter‐patient pharmacokinetics, and a number of factors have been demonstrated to influence absorption, including food intake (specifically a high‐fat meal), gastric pH and frequency of administration (usually three times daily) . To minimise pharmacokinetic variability, gastro‐resistant tablet formulation of PCZ has been developed.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of posaconazole plasma concentrations achieved with the delayed‐release tablets in Korean high‐risk patients with haematologic malignancy

Chae

Cho

et al. 2019

Mycoses

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Summary Background Posaconazole (PCZ) is a triazole approved for prophylaxis of invasive fungal infections. Objectives Herein, the impact of clinical variables on PCZ plasma concentrations (PPCs) attained with PCZ delayed‐release tablet (DRT) was investigated and compared with a historical cohort treated with PCZ oral suspension (OS). Patients/Methods Steady‐state PCZ PPCs in 513 patients with haematologic malignancy treated with PCZ‐DRT were assessed and impact of variables were analysed. Also, a comparison with matched historical cohort treated with PCZ‐OS was made. Results The median PPC in the PCZ‐DRT group was 1,308.9 ng/mL (range: 29.8‐10 455.9). Use of proton pump inhibitor (1181 vs 1344 ng/mL, P = .0337) in the AML/myelodysplastic syndrome remission induction group, diarrhoea (867 vs 1543 ng/mL, P = .0325) and gastrointestinal graft‐versus‐host disease (870 vs 1713 ng/mL, P = .0178) in the HSCT group were associated with lower PPCs. There was lack of evidence that hepatotoxicity was related with PCZ‐DRT. Higher prevalence of UGT1A4*3 allele (33.0%) was noted compared to allele frequency in Koreans in those with PPCs < 500 mg/mL. The median PPC in the PCZ‐DRT group was significantly higher than that in the PCZ‐OS group (1308.9 vs 713.0 ng/mL, P < .0001). Significantly less patients had PPCs < 700 ng/mL in the PCZ‐DRT group compared to the PCZ‐OS group (18.7% vs 48.0%, P < .0001). Conclusions Our study demonstrates that PCZ‐DRT has enhanced absorption and bioavailability than PCZ‐OS in real‐world clinical settings. In addition, specific factors associated with lower PPCs should prompt consideration of therapeutic drug monitoring in patients treated with PCZ‐DRT.

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Determination of posaconazole concentration with LC–MS/MS in adult patients with hematologic malignancy

Cited by 16 publications

References 31 publications

Determination of Posaconazole in Plasma/Serum by High-Performance Liquid Chromatography with Fluorescence Detection

Determination of Posaconazole in Plasma/Serum by High-Performance Liquid Chromatography with Fluorescence Detection

Comparison of Plasma Concentrations of Posaconazole with the Oral Suspension and Tablet in Korean Patients with Hematologic Malignancies

Evaluation of posaconazole plasma concentrations achieved with the delayed‐release tablets in Korean high‐risk patients with haematologic malignancy

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