# Post Mortem Paliperidone Blood Concentrations Following Long-Acting Injectable Treatments

## TL;DR

This study develops a method to measure paliperidone in small blood samples and reports post-mortem concentrations from real cases.

## Contribution

The study introduces a new analytical method for detecting paliperidone in small blood volumes and provides first post-mortem data on paliperidone-treated subjects.

## Key findings

- The developed method showed good linearity, sensitivity, and recovery for paliperidone in whole blood.
- Post-mortem paliperidone concentrations in authentic cases ranged from 23.4 to 146.9 ng/mL.
- Post-mortem concentrations may exceed ante-mortem levels due to redistribution after death.

## Abstract

Background/Objectives: I Paliperidone is an antipsychotic recently added into the market in various formulations. There are few data about safety and on therapeutic, toxic, or lethal blood concentrations. Currently, the published analytical methods are often applied to serum or plasma that are not obtained from cadaveric blood. Alternatively, aliquots of high volume of whole blood are used, but often in forensic investigations using samples at very small quantities. The aims of the present study were (a) to develop an analytical method to detect and quantify paliperidone in whole blood using only a small sample volume (10 µL) and (b) to summarize data on post-mortem blood analysis obtained from authentic autopsy cases. Methods: Method validation was carried out on 10 µL of whole blood, extracted by LLE and analyzed by LC-MS. Paliperidone concentrations obtained from blood analysis of 16 authentic autopsy cases were reported. Results: The method showed a good linearity and sensitivity, a normal distribution, the absence of anomalous values, an interday RSD% always less than 10%, and an 80–120% recovery, as required by AAFS guidelines. Femoral blood concentrations obtained from authentic autopsy cases ranged between 23.4 and 146.9 ng/mL. Conclusions: This method is to be used properly in all cases where it is necessary (a) to monitor the therapeutic adherence of patients, (b) to establish the psycho-physical conditions of the treated subject at the time of the death, and (c) to ascertain if the drug may have played a causal role in the obitus. This study reported the first data obtained from post-mortem investigation of subjects treated with paliperidone LAI. Cadaveric blood concentrations could be higher than ante-mortem reference values due to post-mortem redistribution.