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Drug Metabolite Identification: Stable Isotope Methods
Author(s) -
VandenHeuvel William J. A.
Publication year - 1986
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1986.tb03553.x
Subject(s) - derivatization , metabolite , chemistry , isotope , chromatography , stable isotope ratio , mass spectrometry , drug , pharmacology , biochemistry , biology , physics , quantum mechanics
This paper focuses on (1) stable isotope labeling of drugs, in combination with mass spectrometry (MS)‐based methods, to facilitate the recognition and identification of metabolites and (2) the employment of stable isotope‐labeled derivatization reagents (e.g., bis‐trimethylsilylacetamide‐d 18 ) in the structure elucidation of metabolites from unlabeled drugs via gas‐liquid chromatography‐MS techniques. In both cases, it is the so‐called isotope peak shift that permits generation of data useful for metabolite identification. Furthermore, judicious labeling of a drug permits characterization of drug‐related species (metabolites) by MS‐based recognition of isotope cluster signatures. Studies using stable isotope‐labeled drugs are exemplified by work on aminopyrine and isopropylantipyrine metabolism; examples of the derivatization peak shift approach include those from studies of timolol and cyproheptadine.