Abstract
The advances in high-speed synthesis technologies have produced a large number of biologically active new chemical entities (NCEs) for developability assessment. Current drug discovery efforts have been focused on identifying drug metabolism and pharmacokinetic (DMPK) issues at the earliest possible stage in order to reduce the attrition rate of drug candidates during the development phase. Mass spectrometry (MS) has proven a powerful tool in providing rapid qualitative and quantitative measurements of drug molecules for DMPK studies in both drug discovery and development. Although mass spectrometers can serve as separation devices, for most pharmaceutical applications, some form of chromatography is combined with MS. For most MS-based methods, tandem mass spectrometry (MS/MS) utilizes atmospheric pressure ionization (API) and chromatographic techniques. This review describes the major hyphenated chromatography- mass spectrometry techniques and their applications in supporting exploratory DMPK studies including various in vitro and in vivo PK and metabolite identification profiles.
Current Pharmaceutical Design
Title: The Role of Hyphenated Chromatography-Mass Spectrometry Techniques in Exploratory Drug Metabolism and Pharmacokinetics
Volume: 15 Issue: 19
Author(s): Yunsheng Hsieh and Walter Korfmacher
Affiliation:
Abstract: The advances in high-speed synthesis technologies have produced a large number of biologically active new chemical entities (NCEs) for developability assessment. Current drug discovery efforts have been focused on identifying drug metabolism and pharmacokinetic (DMPK) issues at the earliest possible stage in order to reduce the attrition rate of drug candidates during the development phase. Mass spectrometry (MS) has proven a powerful tool in providing rapid qualitative and quantitative measurements of drug molecules for DMPK studies in both drug discovery and development. Although mass spectrometers can serve as separation devices, for most pharmaceutical applications, some form of chromatography is combined with MS. For most MS-based methods, tandem mass spectrometry (MS/MS) utilizes atmospheric pressure ionization (API) and chromatographic techniques. This review describes the major hyphenated chromatography- mass spectrometry techniques and their applications in supporting exploratory DMPK studies including various in vitro and in vivo PK and metabolite identification profiles.
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Cite this article as:
Hsieh Yunsheng and Korfmacher Walter, The Role of Hyphenated Chromatography-Mass Spectrometry Techniques in Exploratory Drug Metabolism and Pharmacokinetics, Current Pharmaceutical Design 2009; 15 (19) . https://dx.doi.org/10.2174/138161209788682505
DOI https://dx.doi.org/10.2174/138161209788682505 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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