Determination of 7-iodo-1,3-dihydro-1-methyl-5 (2'-fluorophenyl) -2h-1,4-benzodiazepin-2-one (Ro 7-9957) and its major biotransformation products in blood and urine by electron capture-gas-liquid chromatography
Puglishi, C.V.; de Silva, J.A.
Journal of Chromatography 118(3): 370-386
1976
ISSN/ISBN: 0021-9673 PMID: 1254671 Document Number: 110006
A sensitive and specific electron capture-gas chromatographic assay was developed for the determination of 7-ido-1,3-dihydro-1-methyl-5-(2'-fluorophenyl)-2H-1,4-benzodiazepin-2-one (I) and its major metabolites in blood and urine. The overall recovery of I and its N-desmethyl metabolite (II) from blood is apparently quantitative. The recovery of the major urinary metabolite, the N-desmethyl-3-hydroxy analog (IV), and the minor metabolites, the N-desmethyl analog (II) and the N-methyl-3-hydroxy analog (III) added to urine as authentic reference standards ranged from 80-85%. The sensitivity limits of detection are of the order of 2-3 ng of I and 4-5 ng of II /ml of blood or urine. The method was applied to the determination of blood levels and the urinary excretion pattern in a dog following oral and i.v. administration of a 1 mg/kg dose (total 13 mg), and in man following the i.v. administration of single 5- and 10-mg doses. The N-desmethyl metabolite II was more predominant in dog blood than was the orally i.v. administered I, but II was barely measurable in human blood.