Lee, J Son, J Koh, HY Pae, AN Kim, DH 2024-01-21T09:14:05Z 2024-01-21T09:14:05Z 2021-09-03 2003-02-15 0003-2697 https://pubs.kist.re.kr/handle/201004/138819 In vitro metabolic stability of dopamine D-3/D-4 receptor antagonists and identification of their metabolites by high-performance liquid chromatography (HPLC) coupled with ion-trap mass spectrometry (ITMS) were assessed in rat liver microsomes. The compounds were divided into three cassette groups for rapid quantitative analysis of multiple drugs and simultaneous detection of their metabolites. The samples from incubation with rat liver microsomes were pooled into designed cassette groups and analyzed by HPLC/electrospray ITMS in full-scan mode. The metabolic stability of the drugs was determined by comparing their signals after incubation for 0 and for 30 min. The metabolic stability of the examined dopamine receptor antagonists was in the range of 9.9-84.4%. In addition, the present cassette analysis allowed the simultaneous detection of metabolites formed during the same incubation without having to reanalyze the samples. The metabolites were first characterized by nominal mass measurement of the corresponding protonated molecules. Subsequent multistage tandem mass spectrometry on the ion-trap instrument allowed characterization of the structure of the detected metabolites. N,O-dealkylation and ring hydroxylation reactions were identified as major metabolic reactions in piperazinylalkylisoxazole derivatives. These results suggested that the present approach is useful for the rapid evaluation of metabolic stability and structural characterization of metabolites within a short period in new drug discovery. (C) 2003 Elsevier Science (USA). All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE CASSETTE ANALYSIS DRUG DISCOVERY IN-VITRO IDENTIFICATION PREDICTION MICROSOMES CLEARANCE Rapid analysis of metabolic stability of dopamine receptor antagonists and detection of their metabolites by liquid chromatography/tandem mass spectrometry Article 10.1016/S0003-2697(02)00628-0 1 ANALYTICAL BIOCHEMISTRY, v.313, no.2, pp.292 - 300 ANALYTICAL BIOCHEMISTRY 313 2 292 300 scie scopus 000181433300012 2-s2.0-0037442437 Biochemical Research Methods Biochemistry & Molecular Biology Chemistry, Analytical Biochemistry & Molecular Biology Chemistry Article CASSETTE ANALYSIS DRUG DISCOVERY IN-VITRO IDENTIFICATION PREDICTION MICROSOMES CLEARANCE ion-trap mass spectrometry cassette analysis metabolite in vitro metabolic stability