Evaluation of relative LC/MS response of metabolites to parent drug in LC/nanospray ionization mass spectrometry: potential implications in MIST assessment.
There is an increasing demand for quantitative data on metabolite exposure triggered by regulatory guidances. This contribution describes the accuracy of nanoelectrospray ionization mass spectrometry response of drug compounds and their metabolites from biological matrices compared with radiometric quantification. This is a comprehensive investigation of a set of real-life pharmaceutical compounds in relevant matrices such as urine, bile, feces and plasma. The data suggest that nanoelectrospray mass spectrometry can be used for semi-quantitation of metabolites in the absence of reference standards. Therefore, this approach is suitable to screen out non-relevant metabolites early in development as long as an adequate analytical error margin is applied thus balancing risks and resources.
Boehringer Ingelheim Pharma GmbH & Co. KG., Biberach, Germany.
Simone
S
Schadt
Lin-Zhi
LZ
Chen
Daniel
D
Bischoff
D000818:Animals; D001646:Bile / Q000737:chemistry; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000592:standards*; D005243:Feces / Q000737:chemistry; D051379:Mice; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000097:blood / Q000378:metabolism* / Q000652:urine; D051381:Rats; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods* / Q000592:standards; D013552:Swine; D013556:Swine, Miniature
D004364:Pharmaceutical Preparations