Detection and validated quantification of the phosphodiesterase type 5 inhibitors sildenafil, vardenafil, tadalafil, and 2 of their metabolites in human blood plasma by LC-MS/MS--application to forensic and therapeutic drug monitoring cases.

INTRODUCTION: Phosphodiesterase type 5 inhibitors such as sildenafil, vardenafil, and tadalafil are a class of drugs used primarily in the treatment of erectile dysfunction. Sildenafil and tadalafil are also approved for the treatment of pulmonary hypertension. The aim of this study was to develop and validate a procedure for the detection and quantification of these 3 drugs and some of their metabolites in human blood plasma. METHODS: After liquid-liquid extraction of 0.5 mL of blood plasma using diethyl ether-ethyl acetate (1:1), the analytes sildenafil, norsildenafil, vardenafil, norvardenafil, and tadalafil were separated using a Shimadzu Prominence High-Performance Liquid Chromatography System (C18 separation column, gradient elution, and a total flow of 0.5 mL/min). They were detected using an AB Sciex 3200 Q-Trap LC-MS-MS System (electrospray ionization and multiple reaction monitoring mode). The method was fully validated according to international guidelines. RESULTS: The assay was found to be selective for the tested compounds. It was linear from 5 to 1000 ng/mL for sildenafil, from 2 to 700 ng/mL for norsildenafil, from 0.5 to 350 ng/mL for vardenafil, from 0.5 to 200 ng/mL for norvardenafil, and from 5 to 1000 ng/mL for tadalafil. The recoveries were generally more than 50%. Matrix effects were not observed. Accuracy, repeatability, and intermediate precision were within the required limits (<15% or <20% near the limit of quantification). No instability was observed after repeated freezing and thawing or in processed samples. CONCLUSIONS: A liquid chromatography-tandem mass spectrometry assay for the determination of sildenafil, norsildenafil, vardenafil, norvardenafil, and tadalafil in human blood plasma was developed and validated. It has proven to be selective, linear, accurate, and precise for all studied drugs. The method has also proven to be applicable for forensic cases and for therapeutic drug monitoring.

[Modern variant of hanging: use of a time-programmed winch]. / Eine moderne Variante des Erhängens: Einsatz einer zeitprogrammierten Seilwinde.

Hanging is one of the most frequent types of suicide. Descriptions of unusual ligatures can be read about again and again. The paper reports the suicide of a 41-year-old electrician, who, using an electric winch, hung himself in nearly free suspension. The winch that was secured to the timberwork of the attic had been programmed by an electric time clock, the toggle switch of the remote control was fixed in the on-position using adhesive tape. The man had handcuffed his hands behind his back against any attempts to save himself. The noose was partly cushioned with a bike tube with the obvious aim of reducing the pain. Due to the state, in which he was found and the results of the post-mortem examination, a third party responsibility was excluded. The case shows that not only certain types of knots and nooses can be associated with various occupational groups, but the choice of a special strangulation device can possibly also come from the occupational sphere. As a modern variation of hanging, the presented casuistry can partly complete the familiar documentation of historical cases with the use of block and tackle and similar constructions.

[Suicide with exit bags: circumstances and special problem situations in assisted suicide]. / Suizide mit Exit Bags: Umstände und besondere Problemlagen bei Sterbebegleitungen.

So-called exit bags are voluminous, transparent plastic bags, each with a collar to go round the neck, and a Velcro fastening. In conjunction with the consumption of sleeping pills, the bags are recommended as an aid to commit suicide by organizations in favour of "humane death". It is reported on four such suicides by elderly people between 79 and 87 years of age. In two of these cases, there was assistance in committing suicide, one corresponding to a suicide protocol from the Swiss organization for euthanasia, EXIT. In two cases, detailed instructions for committing suicide were found. The morphological findings were not very specific in any of the cases. If the plastic bags are removed by a third party, this type of suicide may remain undetected even after performance of an autopsy. Exit bags tend to be used by older people with either real or feared life-threatening illnesses, in suicides which have usually been planned for some time. From the criminological point of view, the possible active participation of other persons in pulling the covering over the head can often not be proved. Assisting a suicide, in the sense of giving instructions on how to accomplish it, is not punishable in German law.

Unusual suicides of young women with tentative cuts and fatal neck injuries by chain saw and circular saw.

Suicides with chain saws and circular saws are extreme exceptions, in particular with regard to females and concerning the neck region. We report two of such rare cases involving young women. A 30-year-old female with a known schizoaffective psychosis killed herself with an electric chain saw. The autopsy revealed a deep saw cut of the neck and shoulder with partial transection of the cervical spine. Several tentative saw cuts were present on the right lower jaw. A 29-year-old woman suffering from depression committed suicide by use of a circular saw. She inflicted herself fatal neck injuries with at least three separate cutting procedures. Our cases were characterized by the following features: female sex, young adulthood, no occupational experience with saws, psychiatric disorders, absence of alcohol or drugs, use of an aggressive method of suicide, focus of saw injuries on the right side of the neck, detection of tentative saw cuts or several trials, identical causes of death (exsanguination and blood aspiration).