Detection of new metabolites of risperidone in the solid tissues and body fluids obtained from two cadavers by high resolution tandem mass spectrometry

Abstract

Risperidone (Ris) is a second-generation antipsychotic that belongs to the chemical class of benzisoxazole derivatives. 9-Hydroxy (9OH-) Ris is well known among the six reported metabolites of Ris and had been examined using not only blood but also other matrices, but the other five metabolites reported such as benzisoxazole ring-cleaved Ris (c-Ris) and c-9OH-Ris had been detected only in blood, urine and feces. In the present work, large peaks of c-Ris and c-9OH-Ris were detected in the liver, kidney, cerebrum, blood, pericardial fluid, bile and urine obtained from two cadavers. There is a potential that c-Ris and c-9OH-Ris will be good markers to prove Ris consumption in forensic toxicology cases. For example, the peak ratios of c-Ris against the parent Ris in the kidney and blood were as high as 3.9 and 3.6 in cadaver 1; and 7.0 and 7.9 in cadaver 2, respectively. In addition to the previously reported six metabolites, five new metabolites such as dehydrogenated-Ris, 7-keto-Ris and three benzisoxazole ring-cleaved metabolites were disclosed in the present work, and the pathways for the totally eleven metabolites detected in human solid tissues and body fluids have also been proposed, because such pathways were neither reported nor discussed previously.