[1]王 磊,孙文利,刘 瑞,等.HPLC-MS/MS法检测血浆伏立康唑、泊沙康唑和伊曲康唑浓度的方法建立及在白血病患者用药监测中的应用[J].现代检验医学杂志,2019,34(03):10-14.[doi:10.3969/j.issn.1671-7414.2019.03.003]
　WANG Lei,SUN Wen-li,LIU Rui,et al.HPLC-MS/MS Method for the Determination of Plasma Concentrationsof Voriconazole,Posaconazole and Itraconazole and Its Applicationin the Application of Cyclosporine A Monitoring in Leukemia Patients[J].Journal of Modern Laboratory Medicine,2019,34(03):10-14.[doi:10.3969/j.issn.1671-7414.2019.03.003]
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HPLC-MS/MS法检测血浆伏立康唑、泊沙康唑和伊曲康唑浓度的方法建立及在白血病患者用药监测中的应用()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第34卷
期数:
2019年03期
页码:
10-14
栏目:
论著
出版日期:
2019-06-20

文章信息/Info

Title:
HPLC-MS/MS Method for the Determination of Plasma Concentrationsof Voriconazole,Posaconazole and Itraconazole and Its Applicationin the Application of Cyclosporine A Monitoring in Leukemia Patients
文章编号:
1671-7414(2019)03-010-05
作者:
王 磊1; 孙文利1; 刘 瑞1; 王红春1; 刘红星1; 2
(1.河北燕达陆道培医院,河北三河 065201,2.北京陆道培血液病研究院,北京 100176)
Author(s):
WANG Lei1; SUN Wen-li1; LIU Rui1; WANG Hong-chun1; LIU Hong-xing1; 2
(1.Hebei Yanda Lu Daopei Hospital,Hebei Sanhe 065201,China; 2.Beijing Lu Daopei Institute of Hematology,Beijing 100176,China)
关键词:
伏立康唑;  泊沙康唑;  伊曲康唑;  高效液相色谱-串联质谱法;  治疗药物监测
分类号:
Q503; R446.5
DOI:
10.3969/j.issn.1671-7414.2019.03.003
文献标志码:
A
摘要:
目的 建立同时测定白血病患者血浆伏立康唑、泊沙康唑和伊曲康唑浓度的高效液相色谱-串联质谱法(HPLC-MS/MS),并应用于此三种药物的常规治疗药物监测,为其在临床合理使用提供血药浓度依据。方法 色谱柱为Ultimate XB-C18,柱温60℃,流动相:甲醇(0.1 ml/dl甲酸)和水(0.1 ml/dl甲酸和2mmol/L乙酸铵),流速:0.8 ml/min,梯度洗脱。质谱检测方式为电喷雾离子阱正离子模式,MRM扫描,监测伏立康唑m/z 350.1>281.2和伏立康唑-d3 m/z 353.1>284.2; 泊沙康唑 m/z 701.4>683.4和泊沙康唑-d4 m/z 705.4>687.4; 伊曲康唑m/z 705.3>392.2和伊曲康唑-d9 m/z 714.5>401.4。用含伏立康唑、泊沙康唑与伊曲康唑相应同位素内标甲醇液对白血病患者血浆样本进行蛋白沉淀处理,进行质谱检测,内标法定量,对各自检测结果作四分位分析。结果 在0.1～10.0 μg/ml范围内,伏立康唑峰面积/伏立康唑-d3峰面积与伏立康唑浓度线性关系良好,Y=1.58X+0.011 6(R=0.998 7); 泊沙康唑峰面积/泊沙康唑-d4峰面积与泊沙康唑浓度线性关系良好,Y=1.38X+0.021 7(r=0.998 2); 伊曲康唑峰面积/伊曲康唑-d9峰面积与伊曲康唑浓度线性关系良好,Y=1.42X+0.032 5(r=0.999 1)。此三种药物日内及日间相对标准偏差(RSD)均小于5%,平均回收率为95%～105%。1 000份白血病患者伏立康唑浓度四分位结果为Q1～Q3:0.3～1.7 μg/ml; 1 000份白血病患者泊沙康唑浓度四分位结果为Q1～Q3:0.4～1.4μg/ml。结论 建立了同时测定白血病患者伏立康唑、泊沙康唑和伊曲康唑浓度的HPLC-MS/MS法,该方法前处理简单,检测耗时短,检测结果准确度和稳定性好,可适用于临床检测。
Abstract:
Objective HPLC-MS/MS method was established for simultaneous determination of plasma concentrations of voriconazole,posaconazole and itrconazole in leukemia patients,and was applied to the routine drug monitoring of the three drugs,so as to provide the basis of blood drug concentration for their rational use in clinic.Methods Chromatographic column:Ultimate XB-C18,column temperature:60℃,mobile phase:methanol(0.1ml/dl formic acid)and water(0.1 ml/dl formic acid and 2 mmol/L ammoniumacetate ),flow rate:0.8 ml/min,gradient elution.The detection method of mass spectrometry was ESI+,MRM scanning,monitoring voriconazole m/z 350.1>281.2and voriconazol-d3 m/z 353.1>284.2.Posaconazole m/z 701.4>683.4 and posaconazol-d4 m/z 705.4>687.4.Itraconazole m/z 705.3>392.2 and itraconazole-d9 m/z 714.5>401.4.Plasma samples of leukemia patients were treated by proteinprecipitation with methanol containing internal standard of isotopes,and voriconazole,posaconazole and itraconazole were all quantified by internal standardof isotopes.The results of each test were analyzed by quarterwise analysis.Results In the range of 0.1～10.0 μg/ml,there was a goodlinear relationship between voriconazole peak area/voriconazol-d3 peak area andvoriconazole concentration,Y=1.58X+0.011 6(r=0.998 7).There wasa good linear relationship between posaconazole peak area/posaconazole-d4 peakarea and posaconazole concentration,Y=1.38X+0.021 7(r=0.998 2).There was a good linear relationship between itraconazole peak area/itraconazole-d9 peak area and itraconazole concentration,Y=1.42X+0.032 5(r=0.999 1).The intra-day and inter-day RSD of the three drugs were less than 5%,and the average recovery was 95%～105%.The quartile results of voriconazole concentration in 1 000 patients with leukemia were Q1～Q3:0.3 ～1.7 μg/ml.The quartile results of posaconazole concentration in 1 000 patients with leukemia were Q1～Q3:0.4～1.4 μg/ml.Conclusion HPLC-MS/MS methodwas established for simultaneous determination of voriconazole,posaconazole and itraconazole concentrations in leukemia patients.The method has the advantages of simple pretreatment,short detection time,good accuracy and stability,andcan be applied to clinical testing.

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备注/Memo

备注/Memo:
作者简介:王 磊(1984-),男,硕士,助理研究员,主要从事医院药学研究工作,E-mail:rosie1982@163.com。 通讯作者:刘红星,男,硕士,副研究员,主要从事检验医学研究工作。 收稿日期:2019-02-05 修回日期:2019-02-23
更新日期/Last Update: 2019-06-20