Rapid and sensitive characterization of the metabolite formation enzyme kinetics of radiolabeled drugs using stop-flow liquid radiochromatography.
This study evaluated the reproducibility, sensitivity, accuracy, and precision of stop-flow liquid radiochromatographic detection (RFD). Stop-flow RFD was about 10-fold more sensitive compared with traditional RFD and had a good reproducibility for quantification and HPLC retention time. Stop-flow RFD was applied to determine enzyme kinetics of radiolabeled drugs. The enzyme kinetic parameters of muraglitazar glucuronidation determined by stop-flow RFD were comparable with those determined by microplate scintillation counting (MSC).
Zhao
Weiping
W
Bristol-Myers Squibb, Biotransformation, PCO, Princeton, NJ 08540-4000, USA.
Wang
Lifei
L
Zhang
Donglu
D
Zhu
Mingshe
M
D002065:Buspirone / Q000378:metabolism; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D020719:Glucuronides / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D010080:Oxazoles / Q000378:metabolism*; D015203:Reproducibility of Results; D012588:Scintillation Counting / Q000379:methods
C424388:BMS204352; D002250:Carbon Radioisotopes; D020719:Glucuronides; D007211:Indoles; D010080:Oxazoles; D005998:Glycine; D002065:Buspirone; C500085:muraglitazar