Development of a simultaneous quantification method of imatinib and sunitinib and their main metabolites and its application in patients with gastrointestinal stromal tumor

作者全名："Chen, Hefen; Lyu, Jianbo; Gong, Zhujun; Han, Yong; Tao, Kaixiong; Zhou, Hong"

作者地址："[Chen, Hefen; Han, Yong; Zhou, Hong] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Pharm, Wuhan 430022, Peoples R China; [Lyu, Jianbo; Tao, Kaixiong] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Gastrointestinal Surg, Wuhan 430022, Peoples R China; [Gong, Zhujun] Chongqing Med Univ, Dept Pharm, Chongqing, Peoples R China"

通信作者："Zhou, H (通讯作者)，Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Pharm, Wuhan 430022, Peoples R China.; Tao, KX (通讯作者)，Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Gastrointestinal Surg, Wuhan 430022, Peoples R China."

来源：BIOMEDICAL CHROMATOGRAPHY

ESI学科分类：CHEMISTRY

WOS号：WOS:001132130100001

JCR分区：Q3

影响因子：1.8

年份：2024

卷号：38

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：gastrointestinal stromal tumor; imatinib; LC-MS/MS; sunitinib

摘要："Correlations between plasma concentrations of imatinib and sunitinib with efficacy and toxicity have been established. It is crucial to develop a sensitive and precise method for determining the plasma concentrations of imatinib and sunitinib, along with their active metabolites, to facilitate therapeutic drug monitoring and individualized therapy. Plasma samples were separated on an Agilent ZORBAX SB-C18 chromatographic column using gradient elution. Quantification was performed using a mass spectrometer equipped with electrospray ionization in multiple reaction monitoring. The analysis time was 18 min per run, with all analytes and internal standards eluting within 8 min. The calibration range was 25-4000 ng/mL for imatinib, 5-800 ng/mL for N-desmethyl imatinib (CGP74588), and 2.5-400 ng/mL for sunitinib and N-desethyl sunitinib (SU12662). Intra- and inter-assay precision were both below 15%, and accuracy ranged between 90.0% and 101.9%. The method was successfully applied to determine blood samples from 120 patients with gastrointestinal stromal tumors who received imatinib (n = 115) and sunitinib (n = 5). It has been validated as linear, accurate, precise, and robust, making it suitable for therapeutic drug monitoring of imatinib and sunitinib in routine clinical practice."

基金机构："National Natural Science Foundation of China; Young talents project of Hospital Pharmacy Committee of Chinese Pharmaceutical Association [CPA-Z05-ZC-2021-003]; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; [81673456]"

基金资助正文："This project was funded by the Young talents project of Hospital Pharmacy Committee of Chinese Pharmaceutical Association (CPA-Z05-ZC-2021-003) and National Natural Science Foundation of China (81673456). The authors are grateful to the Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, for their assistance in collecting blood samples."