Dianne M Ferry, Pierre L van Zijl, William R Wilson
{"title":"生物样品中碱性DNA插入剂(N,N-二甲氨基乙基)-9-氨基-5-甲基吖啶-4-羧酰胺及其硝基甲基季前药的灵敏液相色谱分析","authors":"Dianne M Ferry, Pierre L van Zijl, William R Wilson","doi":"10.1016/S0378-4347(01)00381-4","DOIUrl":null,"url":null,"abstract":"<div><p>Nitroarylmethyl quaternary (NMQ) ammonium salts of the basic DNA intercalator AMAC (<em>N</em>,<em>N</em>-dimethylaminoethyl-9-amino-5-methylacridine-4-carboxamide) are of interest as anticancer prodrugs. A sensitive HPLC assay has been developed for quantitation of AMAC and its NMQ prodrugs in cultured cells, plasma and tissue. Recovery of the prodrugs, without conversion to AMAC, was achieved using extraction in alkaline acetonitrile followed by immediate reneutralisation. Reversed-phase HPLC with fluorescence detection gave a detection limit of 3 fmol for AMAC, with linearity to 20 nmol (using diode array absorbance at high concentrations). This assay was used to measure cellular uptake, and hypoxic metabolism to AMAC, of three NMQ-AMAC prodrugs.</p></div>","PeriodicalId":15463,"journal":{"name":"Journal of Chromatography B: Biomedical Sciences and Applications","volume":"763 1","pages":"Pages 149-156"},"PeriodicalIF":0.0000,"publicationDate":"2001-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0378-4347(01)00381-4","citationCount":"2","resultStr":"{\"title\":\"Sensitive liquid chromatographic assay for the basic DNA intercalator (N,N-dimethylaminoethyl)-9-amino-5-methylacridine-4-carboxamide and its nitroarylmethyl quaternary prodrugs in biological samples\",\"authors\":\"Dianne M Ferry, Pierre L van Zijl, William R Wilson\",\"doi\":\"10.1016/S0378-4347(01)00381-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Nitroarylmethyl quaternary (NMQ) ammonium salts of the basic DNA intercalator AMAC (<em>N</em>,<em>N</em>-dimethylaminoethyl-9-amino-5-methylacridine-4-carboxamide) are of interest as anticancer prodrugs. A sensitive HPLC assay has been developed for quantitation of AMAC and its NMQ prodrugs in cultured cells, plasma and tissue. Recovery of the prodrugs, without conversion to AMAC, was achieved using extraction in alkaline acetonitrile followed by immediate reneutralisation. Reversed-phase HPLC with fluorescence detection gave a detection limit of 3 fmol for AMAC, with linearity to 20 nmol (using diode array absorbance at high concentrations). This assay was used to measure cellular uptake, and hypoxic metabolism to AMAC, of three NMQ-AMAC prodrugs.</p></div>\",\"PeriodicalId\":15463,\"journal\":{\"name\":\"Journal of Chromatography B: Biomedical Sciences and Applications\",\"volume\":\"763 1\",\"pages\":\"Pages 149-156\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2001-11-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/S0378-4347(01)00381-4\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Chromatography B: Biomedical Sciences and Applications\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378434701003814\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chromatography B: Biomedical Sciences and Applications","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378434701003814","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Sensitive liquid chromatographic assay for the basic DNA intercalator (N,N-dimethylaminoethyl)-9-amino-5-methylacridine-4-carboxamide and its nitroarylmethyl quaternary prodrugs in biological samples
Nitroarylmethyl quaternary (NMQ) ammonium salts of the basic DNA intercalator AMAC (N,N-dimethylaminoethyl-9-amino-5-methylacridine-4-carboxamide) are of interest as anticancer prodrugs. A sensitive HPLC assay has been developed for quantitation of AMAC and its NMQ prodrugs in cultured cells, plasma and tissue. Recovery of the prodrugs, without conversion to AMAC, was achieved using extraction in alkaline acetonitrile followed by immediate reneutralisation. Reversed-phase HPLC with fluorescence detection gave a detection limit of 3 fmol for AMAC, with linearity to 20 nmol (using diode array absorbance at high concentrations). This assay was used to measure cellular uptake, and hypoxic metabolism to AMAC, of three NMQ-AMAC prodrugs.
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