UPLC-MS/MS method for the determination of isavuconazole concentration in plasma of patients with severe infection
10.13699/j.cnki.1001-6821.2024.10.025
- VernacularTitle:用UPLC-MS/MS法测定重症感染患者血浆中艾沙康唑浓度
- Author:
Xiao-Yang LIU
1
;
Bo LI
;
Wen-Qian CHEN
;
Yue CHEN
;
Peng-Mei LI
Author Information
1. 中日友好医院药学部,北京 100029;北京大学药学院临床药学与药事管理学系,北京 100191
- Keywords:
isavuconazole;
ultra-high liquid chromatography-mass spectrometry;
therapeutic drug monitoring;
azole antifungals
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(10):1512-1516
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish and validate a method for the detection of isavuconazole in human plasma by ultra-performance liquid chromatography-mass spectrometry,and apply to blood concentration monitoring to optimize drug treatment regimens.Methods The proteins in plasma samples were precipitated with acetonitrile;isavuconazole-D4 was used as the internal standard.Chromatographic column was ACQUITY UPLC BEH C18(2.1 mm × 50 mnm,1.7 μm),flow phase was 2 mmol·L-1 ammonium acetate-water(containing 0.1％formic acid,A),acetonitrile(containing 0.1％formic acid,B),flow rate was 0.2 mL·min-1,and the column temperature was 40 ℃.Injection volume was 1 μL.The ion pairs were quantitatively analyzed by electro-spray ionization positive ion mode and multiple reaction monitoring,m/z 438.30 → 224.15(isavuconazole),m/z 442.10 → 224.10(isavuconazole-D4).Results The linear range of isavuconazole was 0.31 to 40.00 μg·mL-1(R2=0.999 4);lower limit of quantification(LLOQ)was 0.31 μg·mL-1.The intra-day and inter-day precision ranged from 2.03％to 12.97％and 4.32％to 9.63％,the accuracy deviation ranged from 89.82％to 110.72％and 95.45％to 100.13％,the extraction recovery rates of low,medium and high concentrations ranged from 94.31％to 100.23％.The results of the blood concentrations of 14 patients with clinical use of isavuconazole measured by this method showed that all patients achieved the effective therapeutic concentration of isavuconazole(＞1-2 μg·mL-1).Conclusion This method is fast,sensitive,accurate and stable,It is suitable for detecting the blood concentration of clinical isavuconazole and providing technical guidance for the adjustment of treatment regimen.
