title: Deuterated ritanserin analysis by gas chromatography/mass spectrometry: a sensitive technique to study human ritanserin pharmacokinetics.
abstract: Ritanserin, a new selective serotonin-S2 antagonist, was labelled in one 4-fluorophenyl moiety to obtain a (2H4)-labelled analogue having the following isotopic distribution: 2H0: 0.0%, 2H1: 0.1%, 2H2: 1.9%, 2H3: 5.8%, 2H4: 92.2%. (2H0/2H4) Ritanserin and the internal standard were isolated from the plasma by liquid/liquid extraction and analysed by selected-ion monitoring gas chromatography/mass spectrometry in the 70 eV electron impact mode. A detection limit of 0.1 ng ml-1 could be obtained for both (2H0) and (2H4)ritanserin. The precision (per cent coefficient of variation) and accuracy (per cent relative error) of the method were 4.1% and 4.1%, respectively. The method was used to determine the plasma levels of ritanserin and tetradeuterated ritanserin in three healthy male subjects receiving an equimolar mixture of 5:5 mg (2H0/2H4)ritanserin. The pharmacokinetics of both isotopomers proved to be identical, indicating the absence of an isotope effect, so that this technique might be very promising for use in bioequivalence studies.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Janssen Research Foundation, Beerse, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Timmerman
authors.forename: R
authors.initials: R
authors.lastname: Woestenborghs
authors.forename: H
authors.initials: H
authors.lastname: Lenoir
authors.forename: J
authors.initials: J
authors.lastname: Heykants
mesh_terms: D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007553:Isotope Labeling; D010880:Piperidines / Q000032:analysis* / Q000493:pharmacokinetics; D016713:Ritanserin; D012702:Serotonin Antagonists / Q000032:analysis* / Q000493:pharmacokinetics
chemical_list: D010880:Piperidines; D012702:Serotonin Antagonists; D016713:Ritanserin