代谢分析

LC-MS/MS法同时测定伊马替尼、达沙替尼、尼洛替尼及伏立康唑、伊曲康唑、泊沙康唑的血药浓度

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  • 华中科技大学同济医学院附属同济医院药学部,武汉 430030
第一作者 向 东 Tel: (027)83662329; E-mail:xd9048@sina.com
余恒毅 Tel: (027)83662329; E-mail:434318735@qq.com
*贡雪芃 Tel: (027)83663643; E-mail:1020947167@qq.com
刘 东 Tel: (027)83663643; E-mail:ld2069@outlook.com

收稿日期: 2021-04-02

  网络出版日期: 2024-06-24

Simultaneous determination of imatinib, dasatinib, nilotinib, voriconazole, itraconazole and posaconazole concentration in plasma by LC-MS/MS

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  • Department of Pharmacy, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Received date: 2021-04-02

  Online published: 2024-06-24

摘要

目的: 建立同时测定血浆中3种一线络氨酸激酶抑制剂(伊马替尼、达沙替尼、尼洛替尼)和3种一线三唑类抗真菌药物(伏立康唑、伊曲康唑、泊沙康唑)浓度的液相色谱-串联质谱(LC-MS/MS)方法,并应用于临床进行治疗药物监测。 方法: 血浆样品50 μL加入氯氮平内标 20 μL,采用乙腈直接沉淀蛋白法处理样品后稀释进样分析。采用Welch XB-C18(2.1 mm×50 mm,5.0 μm)色谱柱进行色谱分离,流动相A为10 mol·L-1甲酸铵溶液,流动相B为甲醇-乙腈-异丙醇(7∶1.5∶1.5,含0.2%甲酸),梯度洗脱,流速0.72 mL·min-1, 进样量6 μL, 色谱分析时间3.5 min;采用电喷雾离子源,正离子扫描,多反应监测模式进行测定。 结果: 6种分析物线性范围均满足检测需求,线性系数均≥0.997,各浓度的批内与批间RSD≤10.3%,回收率为98.6%~111.6%,方法准确度为94.3%~109.5%。此外,收集并检测6名同时接受伊马替尼和伏立康唑治疗的白血病患者,血药浓度范围分别为0.418~2.697 μg·mL-1和0.312~8.725 μg·mL-1,个体间差异较大。 结论: 本实验成功建立同时检测3种一线络氨酸酶抑制剂和3种一线三唑类抗真菌药物血药浓度的方法,可应用于临床进行治疗药物监测。

本文引用格式

向东, 余恒毅, 刘璐, 李喜平, 赵婷慧, 李宁红, 刘东, 贡雪芃 . LC-MS/MS法同时测定伊马替尼、达沙替尼、尼洛替尼及伏立康唑、伊曲康唑、泊沙康唑的血药浓度[J]. 药物分析杂志, 2022 , 42(2) : 271 -278 . DOI: 10.16155/j.0254-1793.2022.02.11

Abstract

Objective: To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for a simultaneous determination of three first-line tyrosine kinase inhibitors (imatinib, dasatinib, and nilotinib) and three first-line triazole antifungal drugs (voriconazole, itraconazole, and posaconazole) in plasma, and to use the method in clinical therapeutic drug monitoring. Methods: 50 μL plasma sample was precipitated with acetonitrile after the addition of 20 μL internal standard clozapine and then diluted for analysis. Welch XB-C18 (2.1 mm×50 mm, 5.0 μm) column was used for chromatographic separation. The mobile phase A was 10 mol·L-1 ammonium formate solution and the mobile phase B was methanol-acetonitrile-isopropanol (7∶1.5∶1.5, containing 0.2% formic acid) with gradient elution at the flow rate of 0.72 mL·min-1. The injection volume was 6 μL and the chromatographic time was 3.5 min. Electrospray ion source, positive ion scanning, and multiple reaction monitoring mode were used for determination. Results: The linear range of the six analytes met the detection requirements and the linear coefficients were greater than 0.997. The RSD of intra- and inter-day assays of each concentration was less than 10.34%. The recoveries were 98.6%-111.6% and the accuracy was 94.3%-109.5%. In addition, 6 patients who received imatinib and voriconazole were collected and measured. The plasma concentrations of imatinib and voriconazole were 0.418-2.697 μg·mL-1 and 0.312-8.725 μg·mL-1, respectively, with significant individual differences. Conclusion: This study successfully establishes a method for simultaneously measuring the plasma concentrations of three first-line tyrosine kinase inhibitors and three first-line triazole antifungal drugs, which can be used in clinical therapeutic drug monitoring.

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