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.