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DOI | 10.1021/tx400253k |
Development and Validation of the First Assay Method Coupling Liquid Chromatography with Chemiluminescence for the Simultaneous Determination of Menadione and Its Thioether Conjugates in Rat Plasma | |
Elgawish, Mohamed Saleh1,2; Shimomai, Chikako1; Kishikawa, Naoya1; Ohyama, Kaname1; Wada, Mitsuhiro1; Kuroda, Naotaka1 | |
通讯作者 | Kuroda, Naotaka |
来源期刊 | CHEMICAL RESEARCH IN TOXICOLOGY
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ISSN | 0893-228X |
EISSN | 1520-5010 |
出版年 | 2013 |
卷号 | 26期号:9页码:1409-1417 |
英文摘要 | Menadione (2-methyl-1,4-naphthoquinone, MQ), a component of multivitamin drugs with antihemorrhagic, antineoplastic, and antimalarial activity, is frequently used to investigate quinone-induced cytotoxicity. The formation of MQ conjugates with glutathione (GSH) by Michael addition and subsequent biotransformation to yield N-acetyl-L-cysteine conjugates is believed to be an important detoxification process. However, the resulting conjugates, 2-methyl-3-(glutathione-S-yl)-1,4-naphthoquinone (MQ-GS) and 2-methyl-3-(N-acetyl-L-cysteine-S-y1)-1,4-naphthoquinone (MQ-NAC), retain the ability to redox cycle and to arylate cellular nucleophiles. Although the nephrotoxicity and hepatotoxicity of MQ:thiol conjugates have been reported in vitro, methods for their determination in vivo have yet to be published. Herein, a highly sensitive, simple, and selective HPLC-chemiluminescence (HPLC-CL) coupled method is reported, allowing for the first time the simultaneous determination of MQ MQ-GS, and MQ-NAC in rat plasma after MQ administration. Our method exploits the unique redox characteristics of MQ MQ-GS, and MQ-NAC to react with dithiothreitol (DTT) to liberate reactive oxygen species (ROS) which are detected by a CL assay using luminol as a CL probe. To verify the proposed mechanism, MQ-GS and MQ-NAC were synthetically prepared. Specimen preparation involved solid-phase extraction on an Oasis HLB cartridge followed by isocratic elution on an ODS column. No interference from endogenous substances was detected. Linearity was observed in the range of 5-120 nM for MQ-GS and MQ-NAC and 10-240 nM for MQ, with detection limits (S/N of 3) of 1.4, 0.8, and 128 fmol for MQ:GS, MQNAC, and MQ, respectively. The application of our method reported here is the first to extensively study the stability and reversibility of thiol-quinones. |
类型 | Article |
语种 | 英语 |
国家 | Japan ; Egypt |
收录类别 | SCI-E |
WOS记录号 | WOS:000330095600013 |
WOS关键词 | GLUTATHIONE CONJUGATE ; REACTIVE METABOLITES ; QUINONE-THIOETHERS ; MASS-SPECTROMETRY ; TRANSPORT ; ADDUCTS ; 2-METHYL-1,4-NAPHTHOQUINONE ; METABONOMICS ; INHIBITION ; TOXICOLOGY |
WOS类目 | Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Toxicology |
WOS研究方向 | Pharmacology & Pharmacy ; Chemistry ; Toxicology |
资源类型 | 期刊论文 |
条目标识符 | http://119.78.100.177/qdio/handle/2XILL650/176374 |
作者单位 | 1.Nagasaki Univ, Grad Sch Biomed Sci, Course Pharmaceut Sci, Nagasaki 8528521, Japan; 2.Suez Canal Univ, Fac Pharm, Dept Pharmaceut Chem, Ismailia 41522, Egypt |
推荐引用方式 GB/T 7714 | Elgawish, Mohamed Saleh,Shimomai, Chikako,Kishikawa, Naoya,et al. Development and Validation of the First Assay Method Coupling Liquid Chromatography with Chemiluminescence for the Simultaneous Determination of Menadione and Its Thioether Conjugates in Rat Plasma[J],2013,26(9):1409-1417. |
APA | Elgawish, Mohamed Saleh,Shimomai, Chikako,Kishikawa, Naoya,Ohyama, Kaname,Wada, Mitsuhiro,&Kuroda, Naotaka.(2013).Development and Validation of the First Assay Method Coupling Liquid Chromatography with Chemiluminescence for the Simultaneous Determination of Menadione and Its Thioether Conjugates in Rat Plasma.CHEMICAL RESEARCH IN TOXICOLOGY,26(9),1409-1417. |
MLA | Elgawish, Mohamed Saleh,et al."Development and Validation of the First Assay Method Coupling Liquid Chromatography with Chemiluminescence for the Simultaneous Determination of Menadione and Its Thioether Conjugates in Rat Plasma".CHEMICAL RESEARCH IN TOXICOLOGY 26.9(2013):1409-1417. |
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