Simultaneous determination of sutetinib and its active metabolite sutetinibN-oxide in human plasma by liquid chromatography-tandem mass spectrometry: Evaluation of plasma stability
文献类型：期刊论文
| 作者 | Qiu, Yanan1,2; Tang, Chongzhuang1; Li, Ranran1; Cao, Sumin3; Zhang, Yuqiang3; Chen, Xiaoyan1
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| 刊名 | BIOMEDICAL CHROMATOGRAPHY
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| 出版日期 | 2020-08-13 |
| 页码 | 9 |
| 关键词 | LC-MS MS N-oxide stability sutetinib |
| ISSN号 | 0269-3879 |
| DOI | 10.1002/bmc.4918 |
| 通讯作者 | Chen, Xiaoyan(xychen@simm.ac.cn) |
| 英文摘要 | From the point of view of drug efficacy and safety, pharmacokinetic profiles of both In this work, a sensitive and reliable liquid chromatographic-tandem mass spectrometric method was established for simultaneous determination of sutetinib andN-oxide metabolite (SNO) in human plasma and further applied to a pharmacokinetic study. Analytes were extracted from plasma samples (100 mu l) via acetonitrile-induced protein precipitation and separated on a C(18)column using ammonium acetate with ammonium hydroxide and acetonitrile as the mobile phase. Positive electrospray ionization was carried out through multiple reaction monitoring with transitions ofm/z440.2 -> 367.1 and 446.2 -> 367.1 for sutetinib and SNO, respectively. The method was linear within the concentration range of 0.5-100 ng/ml for both analytes. The precision, accuracy, selectivity, recovery and matrix effect of this method all met the requirements of bioanalytical guidance. In addition, a plasma stability assessment demonstrated unexpected results. Sutetinib was prone to form covalent conjugates with plasma albuminin vitro.The degree of covalent binding increased with increasing temperature, resulting in a significant decrease in its plasma concentrations. However, SNO could not easily bind with albumin owing to steric hindrance or electronegativity. Furthermore, sutetinib and SNO remained stable when blood and plasma samples were kept on wet ice. The validated method was successfully employed for the pharmacokinetic evaluation of sutetinib in patients with advanced malignant solid tumors. |
| WOS关键词 | AFATINIB ; OSIMERTINIB ; ERLOTINIB ; ASSAY |
| 资助项目 | National Natural Science Foundation of China[81573500] ; National Natural Science Foundation of China[81573351] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000558690400001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/292342]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Chen, Xiaoyan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Nanchang Univ, Coll Pharm, Nanchang, Jiangxi, Peoples R China 3.Jiangsu Suzhong Pharmaceut Grp Co Ltd, Taizhou City, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Qiu, Yanan,Tang, Chongzhuang,Li, Ranran,et al. Simultaneous determination of sutetinib and its active metabolite sutetinibN-oxide in human plasma by liquid chromatography-tandem mass spectrometry: Evaluation of plasma stability[J]. BIOMEDICAL CHROMATOGRAPHY,2020:9. |
| APA | Qiu, Yanan,Tang, Chongzhuang,Li, Ranran,Cao, Sumin,Zhang, Yuqiang,&Chen, Xiaoyan.(2020).Simultaneous determination of sutetinib and its active metabolite sutetinibN-oxide in human plasma by liquid chromatography-tandem mass spectrometry: Evaluation of plasma stability.BIOMEDICAL CHROMATOGRAPHY,9. |
| MLA | Qiu, Yanan,et al."Simultaneous determination of sutetinib and its active metabolite sutetinibN-oxide in human plasma by liquid chromatography-tandem mass spectrometry: Evaluation of plasma stability".BIOMEDICAL CHROMATOGRAPHY (2020):9. |
入库方式： OAI收割
来源：上海药物研究所
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