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Application of LC-MS for quantitative analysis and metabolite identification of therapeutic oligonucleotides.
Lin, Zhongping John; Li, Wenkui; Dai, Guowei.
Afiliación
  • Lin ZJ; AstraZeneca Pharmaceuticals LP, Global Development DMPK and Bioanalysis, 1800 Concord Pike, Wilmington, DE 19850, USA. zhongping.lin@astrazeneca.com
J Pharm Biomed Anal ; 44(2): 330-41, 2007 Jun 28.
Article en En | MEDLINE | ID: mdl-17339091
Therapeutic oligonucleotides (OGNs) have been studied extensively in the recent years as novel agents designed to selectively and specifically inhibit target gene expression in cell culture, in animal disease models and in human. This review summarizes applications of liquid chromatography coupled with mass spectrometry or tandem mass spectrometry (LC-MS or LC-MS/MS) for quantitative analysis of therapeutic OGNs and characterization of their metabolism in vitro and in vivo described in the literature over the past 10 years. Although the applications of LC-MS or LC-MS/MS to the molecular mass measurement, sequence determination, DNA adducts identification, detection of mutations and characterization of covalent and/or noncovalent DNA/RNA complexes have been comprehensively reviewed in a few excellent review papers. The quantitative bioanalysis and metabolite identification of therapeutic OGNs using LC-MS or LC-MS/MS have not been covered. This review covers technical issues, current approaches and applications of LC-MS or LC-MS/MS for quantitative analysis of OGNs in biological matrices and characterization of their in vitro and in vivo metabolism. Finally, some conclusions are drawn and prospects of LC-MS in quantitative analysis and metabolism characterization of therapeutic OGNs are discussed.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligonucleótidos / Espectrometría de Masas / Cromatografía Liquida Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: J Pharm Biomed Anal Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligonucleótidos / Espectrometría de Masas / Cromatografía Liquida Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: J Pharm Biomed Anal Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido