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

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.

Quantification of risperidone and paliperidone by liquid chromatography-tandem mass spectrometry in biological fluids and solid tissues obtained from two deceased using the standard addition method.

Risperidone (RIS) is an atypical antipsychotic agent and its 9-hydroxylated metabolite named paliperidone (PAL) also has pharmacological properties similar to that of RIS. Quantifications of RIS and PAL in authentic human biological fluids and solid tissues by liquid chromatography (LC)-tandem mass spectrometry (MS/MS) have not been reported yet although those in plasma (and blood) were reported abundantly. In the present work, a quantification method for RIS and PAL based on the standard addition method was devised and validated for the human fluid and solid tissue specimens. RIS and PAL in biological fluids were quantified only after their dilution and deproteinization. The concentrations of RIS and PAL in the heart whole blood, pericardial fluid, stomach contents, bile, urine, liver, kidney and cerebrum were determined for a deceased who had been treated with RIS therapeutically, and also a deceased who had ingested RIS with other drugs intentionally. To our knowledge, this is the first report on the quantification of RIS and PAL by LC-MS/MS in the authentic human tissues and biological fluids.