Citation: HUAI Bin-Bin, GUO Chun-Na, LI Qiang, GAO Jin, XIE Shun, HUANG Xian-Hui. In vivo Identification of Metabolites of Pyrimethamine in Rats by Liquid Chromatography-Linear Ion Trapped-Orbitrap Mass Spectrometry[J]. Chinese Journal of Analytical Chemistry, ;2016, 44(1): 32-40. doi: 10.11895/j.issn.0253-3820.150309 shu

In vivo Identification of Metabolites of Pyrimethamine in Rats by Liquid Chromatography-Linear Ion Trapped-Orbitrap Mass Spectrometry

1.
College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues, South China Agricultural University, Guangzhou 510640, China

Corresponding author: HUANG Xian-Hui,
Received Date: 17 April 2015
Available Online: 12 September 2015
Fund Project: 本文系农业行业标准制修订项目(No.201391194)资助 (No.201391194)

The metabolism of pyrimethamine (PYR) after a single oral administration at a dose of 5 mg/kg in rats was investigated. In vivo samples including rat plasma, urine and feces were collected respectively at different times. We performed liquid chromatography tandem two-dimensional linear ion trapped orbitrap mass spectrometry spectrometer (LC-LTQ-Orbitrap MS) to identify the unknown metabolites of PYR. Then 10 metabolites of PYR were found in rats with this approach, which indicates that hydroxylation on benzene ring, N-oxidation, dioxidation, N-glucuronidation, methylation+glucuronidation, hydroxylation+glucuronidation and N-oxidation+glucuronidation were the major metabolic pathways of PYR in rats. 9 of these metabolites were identified in vivo for the first time while the PYR 3-N-oxide was ever detected in vitro metabolism of PYR in isolated rat liver. We identified the structure of the metabolites according to their accurate mass data and the characteristic MSn product ions. Based on the above analyses, we proposed the phase I and II metabolic pathways for PYR in rat. The major phase I metabolites were formed via hydroxylation and N-oxidation pathways, and the major phase II metabolites were methylation and glucuronidation.
- Pyrimethamine,
- Rats,
- Liquid chromatography tandem two-dimensional linear ion trapped-orbitrap mass spectrometry,
- Metabolites
1. [1]
  1 Nelson R G, Rosowsky A. Antimicrob Agents Chemother,2001,45(12):3293-3303
2. [2]
  2 Steeve G, Antimicrobial Therapy in Veterinary Medicine. Wiley-Blackwell Press, 2013:293
3. [3]
  3 Satoh K, Kojima N, Furuno M, Kokue E, Hayama T. Congenital Anomalies, 1991,31(4):323-328
4. [4]
  4 Kalla N R, Saggar S K, Puri R, Mehta U. Res. Exp. Med. (Berl), 1997,197(1):45-52
5. [5]
  5 Vijayalaxmi K K, Vishalakshi M. Teratog Carcinog Mutagen, 2000,20(2):65-71
6. [6]
  6 Sullivan G E, Takacs E. Teratology, 1971,4(2):205-209
7. [7]
  7 Peters P J, Thigpen M C, Parise M E, Newman R D. Drug Saf., 2007,30:481-501
8. [8]
  8 Coleman M D, Mihaly G W, Ward S A, Edwards G, Howells R E, Breckenridge A M. Biochem. Pharmacol., 1985,34(12):2193-2197
9. [9]
  9 El-Ghomari K, Gorrod J W. Eur. J. Drug Metab. Pharmacokinet, 1987,12(4):253-258
10. [10]
  10 Junza A, Montane A, Barbosa J, Minguillon C, Barron D. J. Chromatogr. A, 2014,1368:89-99
11. [11]
  11 GUO Yan-Lei, WU Ming-Jun, LI Wen-Juan, JIANG Zheng, YE Fang-Ting, YU Chao. Chinese J. Anal. Chem., 2013,41(7):1074-1079 郭延垒, 吴明军, 李文娟, 江峥, 叶芳挺, 于超.分析化学, 2013,41(7):1074-1079
12. [12]
  12 Caprioli G, Logrippo S, Cahill M G, James K J. Int. J. Food Sci. Nutr., 2014,65(8):942-947
13. [13]
  13 Shan Q, Liu Y, He L, Ding, H, Huang X, Yang F, Li Y, Zeng Z. J. Chromatogr. B, 2012,881-882:96-106
14. [14]
  14 Van Meulebroek L, Bussche J V, Steppe K, Vanhaecke L. J. Chromatogr. A, 2012,1260:67-80
15. [15]
  15 DING Tao, LV Chen, LIU Han, GUO Ling, WU Bin, CHEN Guo-Song, SHEN Chong-Yu, ZHANG Rui, FEI Xiao-Qing, ZHANG Xiao-Yan, YU Jin-Liang. Journal of Instrumental Analysis,2014,33(1):27-32 丁涛, 吕辰, 柳菡, 郭玲, 吴斌, 陈国松, 沈崇钰, 张睿, 费晓庆, 张晓燕, 庾金良.分析测试学报,2014,33(1):27-32
16. [16]
  16 Wang H, Yuan B, Zeng Z, He L, Ding H, Guo C, Kong X, Wang W, Huang X. J. Chromatogr. B, 2014,965:91-99
17. [17]
  17 JIANG Yan-Bin, SHAN Ji-Hao, WANG Ying, CAI Ying-Hua, TIAN Ya-Ping. Chin. J. Pharm. Anal., 2014,(3):385-391 姜艳彬, 单吉浩, 王莹, 蔡英华, 田亚平.药物分析杂志,2014,(3):385-391
18. [18]
  18 Silverman R B. The Organic Chemistry of Drug Design and Drug Action, Translated by GUO Zong-Ru, XIAO Zhi-Yan, LIU Zhan-Zhu, YU Xiao-Ming, XU Bo-Ling, Beijing:Chemical Industry Press,2007:320-322 Silverman R B.有机药物化学(第二版). 郭宗儒, 肖志艳, 刘站柱, 俞晓明, 徐柏玲译. 北京:化学工业出版社, 2007:320-322
1. [1]
  Aidang Lu , Yunting Liu , Yanjun Jiang . Comprehensive Organic Chemistry Experiment: Synthesis and Characterization of Triazolopyrimidine Compounds. University Chemistry, 2024, 39(8): 241-246. doi: 10.3866/PKU.DXHX202401029
2. [2]
  Hao Wu , Zhen Liu , Dachang Bai . ¹H NMR Spectrum of Amide Compounds. University Chemistry, 2024, 39(3): 231-238. doi: 10.3866/PKU.DXHX202309020
3. [3]
  Zhuoming Liang , Ming Chen , Zhiwen Zheng , Kai Chen . Multidimensional Studies on Ketone-Enol Tautomerism of 1,3-Diketones By ¹H NMR. University Chemistry, 2024, 39(7): 361-367. doi: 10.3866/PKU.DXHX202311029
4. [4]
  Zian Lin , Yingxue Jin . Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) for Disease Marker Screening and Identification: A Comprehensive Experiment Teaching Reform in Instrumental Analysis. University Chemistry, 2024, 39(11): 327-334. doi: 10.12461/PKU.DXHX202403066
5. [5]
  Jiaxun Wu , Mingde Li , Li Dang . The R eaction of Metal Selenium Complexes with Olefins as a Tutorial Case Study for Analyzing Molecular Orbital Interaction Modes. University Chemistry, 2025, 40(3): 108-115. doi: 10.12461/PKU.DXHX202405098
6. [6]
  Ke Qiu , Fengmei Wang , Mochou Liao , Kerun Zhu , Jiawei Chen , Wei Zhang , Yongyao Xia , Xiaoli Dong , Fei Wang . A Fumed SiO₂-based Composite Hydrogel Polymer Electrolyte for Near-Neutral Zinc-Air Batteries. Acta Physico-Chimica Sinica, 2024, 40(3): 2304036-0. doi: 10.3866/PKU.WHXB202304036
7. [7]
  Hanmei Lü , Xin Chen , Qifu Sun , Ning Zhao , Xiangxin Guo . Uniform Garnet Nanoparticle Dispersion in Composite Polymer Electrolytes. Acta Physico-Chimica Sinica, 2024, 40(3): 2305016-0. doi: 10.3866/PKU.WHXB202305016
8. [8]
  Rui Li , Huan Liu , Yinan Jiao , Shengjian Qin , Jie Meng , Jiayu Song , Rongrong Yan , Hang Su , Hengbin Chen , Zixuan Shang , Jinjin Zhao . Emerging Irreversible and Reversible Ion Migrations in Perovskites. Acta Physico-Chimica Sinica, 2024, 40(11): 2311011-0. doi: 10.3866/PKU.WHXB202311011
9. [9]
  Rongzhan LOU , Qiaoling KANG , Zhenchao BAI , Dongyun LI , Yang XU , Rui WANG , Qingyi LU . Research progress of sodium ion high entropy layered oxide cathode. Chinese Journal of Inorganic Chemistry, 2025, 41(12): 2411-2428. doi: 10.11862/CJIC.20250142
10. [10]
  Fanpeng Meng , Fei Zhao , Jingkai Lin , Jinsheng Zhao , Huayang Zhang , Shaobin Wang . Optimizing interfacial electric fields in carbon nitride nanosheet/spherical conjugated polymer S-scheme heterojunction for hydrogen evolution. Acta Physico-Chimica Sinica, 2025, 41(8): 100095-0. doi: 10.1016/j.actphy.2025.100095
11. [11]
  Mingyang Men , Jinghua Wu , Gaozhan Liu , Jing Zhang , Nini Zhang , Xiayin Yao . Sulfide Solid Electrolyte Synthesized by Liquid Phase Approach and Application in All-Solid-State Lithium Batteries. Acta Physico-Chimica Sinica, 2025, 41(1): 100004-0. doi: 10.3866/PKU.WHXB202309019
12. [12]
  Xiaotian ZHU , Fangding HUANG , Wenchang ZHU , Jianqing ZHAO . Layered oxide cathode for sodium-ion batteries: Surface and interface modification and suppressed gas generation effect. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 254-266. doi: 10.11862/CJIC.20240260
13. [13]
  Ye Wang , Ruixiang Ge , Xiang Liu , Jing Li , Haohong Duan . An Anion Leaching Strategy towards Metal Oxyhydroxides Synthesis for Electrocatalytic Oxidation of Glycerol. Acta Physico-Chimica Sinica, 2024, 40(7): 2307019-0. doi: 10.3866/PKU.WHXB202307019
14. [14]
  Chunyuan Kang , Xiaoyu Li , Fan Yang , Bai Yang . Ionic-bond crosslinked carbonized polymer dots for tunable and enhanced room temperature phosphorescence. Acta Physico-Chimica Sinica, 2026, 42(1): 100156-0. doi: 10.1016/j.actphy.2025.100156
15. [15]
  Qi Li , Pingan Li , Zetong Liu , Jiahui Zhang , Hao Zhang , Weilai Yu , Xianluo Hu . Fabricating Micro/Nanostructured Separators and Electrode Materials by Coaxial Electrospinning for Lithium-Ion Batteries: From Fundamentals to Applications. Acta Physico-Chimica Sinica, 2024, 40(10): 2311030-0. doi: 10.3866/PKU.WHXB202311030
16. [16]
  Changjun You , Chunchun Wang , Mingjie Cai , Yanping Liu , Baikang Zhu , Shijie Li . Improved Photo-Carrier Transfer by an Internal Electric Field in BiOBr/N-rich C₃N₅ 3D/2D S-Scheme Heterojunction for Efficiently Photocatalytic Micropollutant Removal. Acta Physico-Chimica Sinica, 2024, 40(11): 2407014-0. doi: 10.3866/PKU.WHXB202407014
17. [17]
  Lina Guo , Ruizhe Li , Chuang Sun , Xiaoli Luo , Yiqiu Shi , Hong Yuan , Shuxin Ouyang , Tierui Zhang . Effect of Interlayer Anions in Layered Double Hydroxides on the Photothermocatalytic CO₂ Methanation of Derived Ni-Al₂O₃ Catalysts. Acta Physico-Chimica Sinica, 2025, 41(1): 100002-0. doi: 10.3866/PKU.WHXB202309002
18. [18]
  Nan Wu , Hang Zhang , Lingling Wei , Quan Gu , Haoquan Zheng , Weiqiang Zhang , Rui Cao . Cyanide: Poison or Treasure?. University Chemistry, 2025, 40(7): 177-188. doi: 10.12461/PKU.DXHX202409072
19. [19]
  Zhaoxuan ZHU , Lixin WANG , Xiaoning TANG , Long LI , Yan SHI , Jiaojing SHAO . Application of poly(vinyl alcohol) conductive hydrogel electrolytes in zinc ion batteries. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 893-902. doi: 10.11862/CJIC.20240368
20. [20]
  Zhi Dou , Huiyu Duan , Yixi Lin , Yinghui Xia , Mingbo Zheng , Zhenming Xu . High-Throughput Screening Lithium Alloy Phases and Investigation of Ion Transport for Solid Electrolyte Interphase Layer. Acta Physico-Chimica Sinica, 2024, 40(3): 2305039-0. doi: 10.3866/PKU.WHXB202305039

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(586)
HTML views(27)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142