Gesetzesentwurf zur Änderung des Bundesnaturschutzgesetzes und weiterer Rechtsvorschriften

Keine Zusammenfassung     

The time-dependant post-mortem redistribution of antipsychotic drugs

The post mortem redistribution of ten commonly prescribed antipsychotic drugs (APs) was investigated. Femoral blood was collected from 273 cases at admission to mortuary (AD) and at post-mortem (PM). The PM samples were collected at various times up to nine days after admission and the sample pairs analysed using LC-MS/MS. The drugs included in this study were 9OH-risperidone (paliperidone), amisulpride, chlorpromazine, clozapine, haloperidol, olanzapine, promethazine, quetiapine, risperidone, and zuclopenthixol. Haloperidol, quetiapine and risperidone showed minimal changes between AD and PM specimens, whereas the majority of drugs showed significant changes between the sample pairs collected at different time points post mortem (p<0.01) in addition to an average concentration change greater than the uncertainty of measurement of the applied method. Average increases in blood concentrations after admission to the mortuary ranged up to 112% (chlorpromazine and olanzapine) but also decreases up to -43% (9OH-risperidone) were seen. There were large standard deviations between sample pairs and substantial day-to-day unpredictable changes that highlight the difficulty in the interpretation of drug concentrations post-mortem. Based on the presented data, we recommend that specimens for toxicological analysis should to be taken as soon as possible after admission of a deceased person to the mortuary in order to minimise the effects of the PM interval on the drug concentration in blood.     

Identification of 2-hydroxymethyl-olanzapine as a novel degradation product of olanzapine

Olanzapine (OLZ) is amongst the most commonly prescribed antipsychotic drugs and is associated with substantial instability. The aim of this study was to investigate the instability of OLZ and to identify the degradants formed from its breakdown. Three experiments were conducted to monitor the degradation of OLZ and the formation of degradants in blood (1), water (2), and post-extraction at 4 °C (3). All three sample sets were analysed in duplicate and repeated in the absence (A) and presence (B) of 0.25% ascorbic acid. One degradant was identified in sample sets 2A and 3A with m/z 329 and confirmed as 2-hydroxymethyl-OLZ (2-OH-OLZ) using LC-MS techniques. The addition of 0.25% ascorbic acid slowed the degradation of OLZ down in all three experiments and inhibited the formation of 2-OH-OLZ in sample sets 2A and 3A. To investigate the influence of oxygen on the degradation of OLZ and the formation of 2-OH-OLZ in water, an additional experiment (4) was conducted. Sample sets were prepared containing different vortexing or sonication steps in order to alter the oxygen content in the samples. Statistical analysis confirmed that degradation increased significantly following vortexing for 1 min while sonication did not affect the rate of degradation of OLZ further suggesting the involvement of oxygen in the degradative processes. 2-OH-OLZ was only identified as a degradant of OLZ in aqueous solutions. It also degrades over time but its product is currently unknown and is under investigation.