Enantioselective Determination of Ondansetron and 8-Hydroxyondansetron in Human Plasma from Recovered Surgery Patients by Liquid Chromatography-Tandem Mass Spectrometry

A liquid chromatographic-mass spectrometric assay with atmospheric pressure chemical ionization for quantification of ondansetron and its main metabolite 8-hydroxyondansetron in human plasma was presented. The enantiomeric separation was achieved on a Chiralcel OD-R column containing cellulose tris-(3,5-dimethylphenylcarbamate). The validation data were within the required limits. The assay was successfully applied to authentic plasma samples. Quantitative results from postoperative patients receiving ondansetron demonstrated a great interindividual variability in postoperative plasma drug concentrations, the metabolites were not detected in their unconjugated form. A wide variation in the S-(+)-/R-(−)-ondansetron concentration ratio between 0.14 and 7.18 is indicative for a stereoselective disposition or metabolism. In further studies CYP2D6 and CYP3A4 genotype dependent metabolism of ondansetron enantiomers as well as of co-administered drugs and clinical efficacy of the medication should be teste

A new simulation-based model for calculating post-mortem intervals using developmental data for Lucilia sericata (Dipt.: Calliphoridae)

Homicide investigations often depend on the determination of a minimum post-mortem interval (PMI$_{min}$) by forensic entomologists. The age of the most developed insect larvae (mostly blow fly larvae) gives reasonably reliable information about the minimum time a person has been dead. Methods such as isomegalen diagrams or ADH calculations can have problems in their reliability, so we established in this study a new growth model to calculate the larval age of \textit{Lucilia sericata} (Meigen 1826). This is based on the actual non-linear development of the blow fly and is designed to include uncertainties, e.g. for temperature values from the crime scene. We used published data for the development of \textit{L. sericata} to estimate non-linear functions describing the temperature dependent behavior of each developmental state. For the new model it is most important to determine the progress within one developmental state as correctly as possible since this affects the accuracy of the PMI estimation by up to 75%. We found that PMI calculations based on one mean temperature value differ by up to 65% from PMIs based on an 12-hourly time temperature profile. Differences of 2\degree C in the estimation of the crime scene temperature result in a deviation in PMI calculation of 15 - 30%.Comment: 14 pages, 5 figures, 1 tabl

Sharing of heteroplasmies between human liver lobes varies across the mtDNA genome

Mitochondrial DNA (mtDNA) heteroplasmy (intra-individual variation) varies among different human tissues and increases with age, suggesting that the majority of mtDNA heteroplasmies are acquired, rather than inherited. However, the extent to which heteroplasmic sites are shared across a tissue remains an open question. We therefore investigated heteroplasmy in two liver samples (one from each primary lobe) from 83 Europeans, sampled at autopsy. Minor allele frequencies (MAF) at heteroplasmic sites were significantly correlated between the two liver samples from an individual, with significantly more sharing of heteroplasmic sites in the control region than in the non-control region. We show that this increased sharing for the control region cannot be explained by recent mutations at just a few specific heteroplasmic sites or by the possible presence of 7S DNA. Moreover, we carried out simulations to show that there is significantly more sharing than would be predicted from random genetic drift from a common progenitor cell. We also observe a significant excess of non-synonymous vs. synonymous heteroplasmies in the protein-coding region, but significantly more sharing of synonymous heteroplasmies. These contrasting patterns for the control vs. the non-control region, and for non-synonymous vs. synonymous heteroplasmies, suggest that selection plays a role in heteroplasmy sharing

Reliability Analysis on the Effect of Subsea Buoy to the Tension of Spread Mooring System

A lot of research has been carried out regarding variations in mooring systems, one of which is the addition of buoys to the mooring system. In analyzing variations in mooring system designs, what needs to be considered is the reliability of the mooring lines. Therefore, in this research will analyze reliability on the effect of subsea buoy to the tension of mooring line with a variation position of subsea buoy. The variations on the position of one subsea buoy is arranged at the distance of the anchor 605 m, 577.5 m, 550 m, 522.5 and two subsea buoys at the distance from the anchor 605 m and 467.5 m. The analysis was performed for stand alone and offloading conditions with wave directions of 0 °, 45 °, 90 °, 135 °, 180 °. In this study to find the reliability of mooring lines, the author uses the Mean Value First Order Second Moment (MVFOSM) method. The results from this study, the probability of failure in the offloading condition without subsea buoy is 4.897E-17 and with subsea buoy (522.5 m) is 4.018E-17. Probability of failure in the stand alone condition without subsea buoy is 2.763E-16 and with subsea buoy (522.5 m) is 1.881E-16. From the probability of failure, the reliability of mooring lines in the offloading condition and stand alone condition without subsea buoy and with subsea buoy (522.5 m) is 1.00. The reliability calculation determined by DNV-OS E301, the results obtained meet the specified reliability criteria

Enantioselective determination of ondansetron and 8-hydroxyondansetron in human plasma from recovered surgery patients by liquid chromatography-tandem mass spectrometry

A liquid chromatographic-mass spectrometric assay with atmospheric pressure chemical ionization for quantification of ondansetron and its main metabolite 8-hydroxyondansetron in human plasma was presented. The enantiomeric separation was achieved on a Chiralcel OD-R column containing cellulose tris-(3,5-dimethylphenylcarbamate). The validation data were within the required limits. The assay was successfully applied to authentic plasma samples. Quantitative results from postoperative patients receiving ondansetron demonstrated a great interindividual variability in postoperative plasma drug concentrations, the metabolites were not detected in their unconjugated form. A wide variation in the S-(+)-/R-(-)-ondansetron concentration ratio between 0.14 and 7.18 is indicative for a stereoselective disposition or metabolism. In further studies CYP2D6 and CYP3A4 genotype dependent metabolism of ondansetron enantiomers as well as of co-administered drugs and clinical efficacy of the medication should be tested

European Council of Legal Medicine (ECLM) on-site inspection forms for forensic pathology, anthropology, odontology, genetics, entomology and toxicology for forensic and medico-legal scene and corpse investigation: the Parma form

Further to a previous publication by the European Council of Legal Medicine (ECLM) concerning on-site forensic and medico-legal scene and corpse investigation, this publication provides guidance for forensic medical specialists, pathologists and, where present, coroners’ activity at a scene of death inspection and to harmonize the procedures for a correct search, detection, collection, sampling and storage of all elements which may be useful as evidence, and ensure documentation of all these steps. This ECLM’s inspection form provides a checklist to be used on-site for the investigation of a corpse present at a crime or suspicious death scene. It permits the collection of all relevant data not only for the pathologist, but also for forensic anthropologists, odontologists, geneticists, entomologists and toxicologists, thus supporting a collaborative work approach. Detailed instructions for the completion of forms are provided