Determination of voriconazole and its N-oxide in human plasma by LC-MS/MS and its clinical application
- Journal of Third Military Medical University Vol. 41, Issue 15, Pages: 1478-1484(2019)
- 作者机构：
- 作者简介：
- 基金信息：the Science and Technology Innovation Special Project of Social Undertakings and People's Livelihood Security of Chongqing(CSTC2017shmsA130043);the Project of the First Affiliated Hospital of Army Medical University(SWH2014LC03)
DOI：10.16016/j.1000-5404.201902067
CLC：Received：19 February 2019，
Published：15 August 2019
- 稿件说明：
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Rongfeng XIANG, Shenglan SHANG, Lirong XIONG, et al. Determination of voriconazole and its N-oxide in human plasma by LC-MS/MS and its clinical application[J]. Journal of Third Military Medical University, 2019, 41(15): 1478-1484.
Rongfeng XIANG, Shenglan SHANG, Lirong XIONG, et al. Determination of voriconazole and its N-oxide in human plasma by LC-MS/MS and its clinical application[J]. Journal of Third Military Medical University, 2019, 41(15): 1478-1484. DOI： 10.16016/j.1000-5404.201902067.
摘要
Abstract
Objective
2
To develop liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the content determination of voriconazole (VRCZ) and its N-oxide (VNO) in human plasma
and to apply it to clinical samples.
Methods
2
Ketoconazole was used as the internal standard (IS). The plasma samples were treated with methanol to precipitate protein and analyzed by HPLC-MS/MS. The detection was accomplished with electrospray ionization (ESI) operated in positive ionization mode
and ion reaction pairs were selected to be m/z350.1→m/z127.0 (VRCZ)
m/z366.1→m/z224.0 (VNO) and m/z531.0→m/z82.1 (Ketoconazole). Chromatographic separation had been achieved on Inertsil ODS-3 (50/2.1) with methanol-10 mmol/L ammonium acetate (90:10) as the mobile phase. Plasma concentrations of VRCZ and VNO in 23 patients were determined.
Results
2
Both VRCZ and VNO were linear (r>0.999) over the concentration ranges of 0.4~10.0 μg/mL
inter- and intra-batch relative standard deviations (RSDs) and matrix effect were all less than 15%. The 2 compounds remained stable during sample storage and handling progress. Plasma concentrations of VRCZ in 23 patients ranged from 0.4 to 14.3 μg/mL
and those of VNO ranged from 0.5 to 7.2 μg/mL. Significant variance was found among these patients.
Conclusion
2
LC-MS/MS is simple
quick and sensitive for detection of VRCZ and VNO
and can be used for drug monitoring in clinical practice.
关键词
Keywords
references
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