Simultaneous determination of unecritinib (TQ-B3101) and its active metabolite crizotinib in rat plasma by LC-MS/MS:An application to pharmacokinetic studies
文献类型：期刊论文
| 作者 | Wang, Hong2,3; Chen, Huixian2,3; Cui, Xinran1; Zhang, Yuchen2,3; Zhou, Jialan3; Chen, Xiaoyan1,2,3
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| 刊名 | JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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| 出版日期 | 2024-08-15 |
| 卷号 | 246页码:9 |
| 关键词 | Unecritinib (TQ-B3101) Crizotinib Carboxylesterases LC-MS/MS Hydrolytic metabolism |
| ISSN号 | 0731-7085 |
| DOI | 10.1016/j.jpba.2024.116199 |
| 通讯作者 | Chen, Xiaoyan(xychen@simm.ac.cn) |
| 英文摘要 | Unecritinib (TQ-B3101) is a selective tyrosine kinase receptor inhibitor. In the study, in vitro metabolic experiments revealed that the hydrolysis of TQ-B3101 was mainly catalyzed by carboxylesterase 2 (CES2), followed by CES1. Next, a sensitive and reliable LC-MS/MS method was established for the simultaneous determination of TQ-B3101 and its metabolite crizotinib in rat plasma. To prevent in vitro hydrolysis of TQ-B3101, sodium fluoride, the CESs inhibitor at a concentration of 2 M, was immediately added after whole blood collection. Plasma samples were extracted by acetonitrile-induced protein precipitation method, and chromatographically separated on a Gemini C-18 column (50 mm x 2.0 mm i.d., 5 mu m) using gradient elution with a mobile phase of 0.1% formic acid and 5 mmol/L ammonium acetate with 0.1% formic acid. The retention times for TQ-B3101 and crizotinib were 2.61 and 2.38 min, respectively. The analytes were detected with tandem mass spectrometer by positive electrospray ionization, using the ion transitions at m/z 492.3 -> 302.3 for TQ-B3101, m/z 450.3 -> 260.3 for crizotinib, and m/z 494.0 -> 394.3 for imatinib (internal standard). Method validation was conducted in the linear range of 1.00-800 ng/mL for the two analytes. The precision, accuracy and stabilities all met the acceptance criteria. The pharmacokinetic study indicated that TQ-B3101 was rapidly hydrolyzed to crizotinib with the elimination half-life of 1.11 h after a single gavage administration of 27 mg/kg to Sprague-Dawley rats, and the plasma exposure of TQ-B3101 was only 2.98% of that of crizotinib. |
| WOS关键词 | CELL LUNG-CANCER ; ESTERASE INHIBITOR ; CARBOXYLESTERASES ; MANAGEMENT ; STABILITY |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001242748000001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/311618]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Xiaoyan |
| 作者单位 | 1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Hong,Chen, Huixian,Cui, Xinran,et al. Simultaneous determination of unecritinib (TQ-B3101) and its active metabolite crizotinib in rat plasma by LC-MS/MS:An application to pharmacokinetic studies[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2024,246:9. |
| APA | Wang, Hong,Chen, Huixian,Cui, Xinran,Zhang, Yuchen,Zhou, Jialan,&Chen, Xiaoyan.(2024).Simultaneous determination of unecritinib (TQ-B3101) and its active metabolite crizotinib in rat plasma by LC-MS/MS:An application to pharmacokinetic studies.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,246,9. |
| MLA | Wang, Hong,et al."Simultaneous determination of unecritinib (TQ-B3101) and its active metabolite crizotinib in rat plasma by LC-MS/MS:An application to pharmacokinetic studies".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 246(2024):9. |
入库方式： OAI收割
来源：上海药物研究所
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