A simple isotope-labeled UHPLC-MS/MS assay for simultaneous quantification of methotrexate, imatinib and dasatinib

被引:1
作者
Zhang, Yao [1 ]
Liu, Yao [2 ]
Tan, Lu [1 ]
机构
[1] Southern Med Univ, Affiliated Hosp 3, Dept Pharm, Guangzhou 510630, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 5, Dept Pharm, Zhuhai 519000, Peoples R China
关键词
dasatinib; imatinib; methotrexate; therapeutic drug monitoring; UHPLC-MS; MS; ACUTE LYMPHOBLASTIC-LEUKEMIA; HIGH-DOSE METHOTREXATE; CHILDREN; PHARMACOKINETICS;
D O I
10.4155/bio-2021-0162
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Aim: To assist therapeutic dose adjustment in clinic, a reliable concentration measurement is quite necessary for therapeutic drug monitoring. Results: A UHPLC-MS/MS bioassay for simultaneous determination of methotrexate, imatinib and dasatinib using isotope dilution internal standardization has been established and fully validated as per China Food and Drug Administration guideline. After a simple protein precipitation, the analytes were separated by a gradient elution within 3 min and mass detection was performed via ESI+ mode with SRM. The calibration curves were in the range of 5-100 ng/ml for methotrexate, 25-5000 ng/ml for imatinib and 1-250 ng/ml for dasatinib. Imprecision and inaccuracy values were <= 9.44% and <= 12.81% for all analytes, respectively. Conclusion: The developed method is appropriate for therapeutic drug monitoring, being applied to help individualized therapy in patients with acute lymphoblastic leukemia.
引用
收藏
页码:1501 / 1510
页数:10
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