Qualitative and quantitative determination of SIPI-2011 and its two major metabolites in human plasma
文献类型：期刊论文
| 作者 | Fang, Jie2,3; Jing, Jiao1; Li, Guangyao2,3; Wang, Yongbin2,3; Zhao, Binjiang1; Zhan, Yan2 ; Zhou, Lei2; Liu, Ying2; Zhang, Wei1; Peng, Ni2
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| 刊名 | JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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| 出版日期 | 2025-10-15 |
| 卷号 | 264页码:11 |
| 关键词 | SIPI-2011 UPLC-UV/Q-TOF LC-MS/MS Metabolic Profiling Pharmacokinetics |
| ISSN号 | 0731-7085 |
| DOI | 10.1016/j.jpba.2025.116958 |
| 英文摘要 | SIPI-2011, a structural modification of isoquinoline alkaloid, is under investigation for treating arrhythmias. To characterize the safety and tolerability, the pharmacokinetics and metabolism of SIPI-2011 were investigated in humans. After an oral administration of 600 mg SIPI-2011, a total of 32 metabolites were detected in human plasma by UPLC-UV/Q-TOF mass spectrometry utilizing mass defect filter method. The principal biotransformation pathways included di-dehydrogenation (M8-1), dehydrogenation (M9-2), and oxidation and dehydrogenation (M10-4). Afterward, a sensitive LC-MS/MS method was developed to simultaneously determine SIPI-2011 and its two major metabolites M8-1 and M9-2 in human plasma. The isotopically labeled internal standards of the metabolites were obtained by incubating deuterated SIPI-2011 with rat liver homogenates. To achieve effective chromatographic retention and separation, three analytes were eluted on an XDB-phenyl column with alkaline mobile phase, and detected by multiple reaction monitoring (MRM) with positive electrospray ionization source. To reduce the interference from the isotope signals of M8-1 and M9-2 in the higher calibration point, [M+H+ 1]+ ions were selected as precursor ions of M9-2 and SIPI-2011 for MRM analysis. The assay was linear in the concentration range 15.0-3000 ng/mL for SIPI-2011, 0.500-100 ng/mL for M8-1 and 1.00-200 ng/ mL for M9-2. The parameters of the method validation all met the acceptance criteria. The pharmacokinetic study indicated that SIPI-2011 was rapidly absorbed with a median Tmax of 0.65 h and a terminal half-life of 15.4 h when healthy volunteers were administered a single dose of 300 mg SIPI-2011. And the plasma exposures of the two metabolites M8-1 and M9-2 were less than 10 % of that of the parent drug. |
| WOS关键词 | LIQUID-CHROMATOGRAPHY ; CLASSIFICATION ; HIGENAMINE ; BERBERINE ; DIAGNOSIS ; URINE |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001498391700003 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318270]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Xiaoyan |
| 作者单位 | 1.Jiangsu Kan Pharmaceut Co Ltd, State Key Lab Technol Chinese Med Pharmaceut Proc, Lianyungang 222047, Jiangsu, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fang, Jie,Jing, Jiao,Li, Guangyao,et al. Qualitative and quantitative determination of SIPI-2011 and its two major metabolites in human plasma[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2025,264:11. |
| APA | Fang, Jie.,Jing, Jiao.,Li, Guangyao.,Wang, Yongbin.,Zhao, Binjiang.,...&Chen, Xiaoyan.(2025).Qualitative and quantitative determination of SIPI-2011 and its two major metabolites in human plasma.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,264,11. |
| MLA | Fang, Jie,et al."Qualitative and quantitative determination of SIPI-2011 and its two major metabolites in human plasma".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 264(2025):11. |
入库方式： OAI收割
来源：上海药物研究所
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