Quantification of Usaramine and its N-Oxide Metabolite in Rat Plasma Using Liquid Chromatography-Tandem Mass Spectrometry
文献类型：期刊论文
| 作者 | Lin, Feifei2,3 ; Ma, Yan1; Pan, Anni2; Ye, Yang2,3; Liu, Jia2
|
| 刊名 | JOURNAL OF ANALYTICAL TOXICOLOGY
 |
| 出版日期 | 2021-06-19 |
| 卷号 | 46期号:5页码:512-518 |
| ISSN号 | 0146-4760 |
| DOI | 10.1093/jat/bkab060 |
| 通讯作者 | Ye, Yang(yye@simm.ac.cn) ; Liu, Jia(jia.liu@simm.ac.cn) |
| 英文摘要 | A sensitive, fast and robust liquid chromatography--tandem mass spectrometry (LC-MS-MS) method was developed and validated for the determination of usaramine (URM) and usaramine N-oxide (UNO) in rat plasma. The separation was conducted on an ACQUITY UPLC BEH C-18 Column (50 x 2.1 mm, 1.7 mu m) and gradient eluted with mobile phase A (0.1% formic acid with 5 mM ammonium acetate in water) and B (0.1% formic acid in acetonitrile/methanol, 9/1, v/v). The method was linear over the range of 1-2,000 ng/mL for both analytes. The validated method was applied to investigate the pharmacokinetic behaviors and sex differences of URM and its N-oxide metabolite in rats. After intravenous administration of URM at 1 mg/kg, the AUC(0-t) values for URM and UNO were 363 +/- 65 and 172 +/- 32 ng/mL*h in male rats, while 744 +/- 122 and 30.7 +/- 7.4 ng/mL*h in females, respectively. The clearance of URM was significantly higher in male rats than in females (2.77 +/- 0.50 vs 1.35 +/- 0.19 L/h/kg, P < 0.05). After oral administration of URM at 10 mg/kg, the AUC(0-t) values of URM and UNO were 1,960 +/- 208 and 1,637 +/- 246 ng/mL*h in male rats, while 6,073 +/- 488 and 300 +/- 62 ng/mL*h in females, respectively. The oral bioavailability of URM in female rats (81.7%) was much higher than in males (54.0%). In conclusion, sex-based differences were observed in the pharmacokinetics, N-oxide metabolism and oral bioavailability of URM. |
| WOS关键词 | PYRROLIZIDINE ALKALOID SENECIONINE ; SINUSOIDAL OBSTRUCTION SYNDROME ; LIVER ; CLIVORINE ; INDUCTION ; PLANTS ; CYP3A ; DNA |
| 资助项目 | Science and Technology Commission of Shanghai Municipality[19431908100] |
| WOS研究方向 | Chemistry ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000798356900001 |
| 出版者 | OXFORD UNIV PRESS INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/301080]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Ye, Yang; Liu, Jia |
| 作者单位 | 1.Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Med, 536 Changle Rd, Shanghai 200126, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Ave, Nanjing 210023, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lin, Feifei,Ma, Yan,Pan, Anni,et al. Quantification of Usaramine and its N-Oxide Metabolite in Rat Plasma Using Liquid Chromatography-Tandem Mass Spectrometry[J]. JOURNAL OF ANALYTICAL TOXICOLOGY,2021,46(5):512-518. |
| APA | Lin, Feifei,Ma, Yan,Pan, Anni,Ye, Yang,&Liu, Jia.(2021).Quantification of Usaramine and its N-Oxide Metabolite in Rat Plasma Using Liquid Chromatography-Tandem Mass Spectrometry.JOURNAL OF ANALYTICAL TOXICOLOGY,46(5),512-518. |
| MLA | Lin, Feifei,et al."Quantification of Usaramine and its N-Oxide Metabolite in Rat Plasma Using Liquid Chromatography-Tandem Mass Spectrometry".JOURNAL OF ANALYTICAL TOXICOLOGY 46.5(2021):512-518. |
入库方式： OAI收割
来源：上海药物研究所
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