New Methods Used in Pharmacokinetics and Therapeutic Monitoring of the First and Newer Generations of Antiepileptic Drugs (AEDs)

The review presents data from the last few years on bioanalytical methods used in therapeutic drug monitoring (TDM) of the 1st–3rd generation and the newest antiepileptic drug (AEDs) cenobamate in patients with various forms of seizures. Chemical classification, structure, mechanism of action, pharmacokinetic data and therapeutic ranges for total and free fractions and interactions were collected. The primary data on bioanalytical methods for AEDs determination included biological matrices, sample preparation, dried blood spot (DBS) analysis, column resolution, detection method, validation parameters, and clinical utility. In conclusion, the most frequently described method used in AED analysis is the LC-based technique (HPLC, UHPLC, USLC) combined with highly sensitive mass detection or fluorescence detection. However, less sensitive UV is also used. Capillary electrophoresis and gas chromatography have been rarely applied. Besides the precipitation of proteins or LLE, an automatic SPE is often a sample preparation method. Derivatization was also indicated to improve sensitivity and automate the analysis. The usefulness of the methods for TDM was also highlighted

Causes of Death during the Intravenous Infusion of Dimethylsulphoxide and Hydrogen Peroxide in the Course of Alternative Medicine Therapy

Unconventional (alternative, natural) medicine in Poland and worldwide includes hundreds of non-scientifically verified “treatment” modalities. Among the most popular are biological therapies using chemical or natural compounds administered with injection or drip infusion. The latter has found the most excellent use in treating rheumatological and dermatological diseases and certain types of cancer. Vitamin infusions, curcumin, glutathione, perhydrol and dimethylsulphoxide (DMSO) have gained popularity among clients of natural medicine clinics. The present study aims to analyse the case of a 37-year-old woman who was administered infusions containing perhydrol and DMSO (0.5 mL 0.04% hydrogen peroxide/0.5 mL p.d.a DMSO in saline) due to a MTHFR A1298C mutation. After having the next infusion, the woman complained of nausea and then became unconscious. Subsequently, she suffered respiratory and cardiac arrest. Adequate resuscitation was undertaken. After being taken to the hospital, the patient was in critical condition and died due to increasing multiple-organ failure. Initially, there was suspected DMSO poisoning as it was the only compound to have been administered as an intravenous infusion. However, it was not until the analysis of the secured evidence that it became clear that the patient had also been given an intravenous solution of hydrogen peroxide, H2O2, and that there had been a mistake in preparing the intravenous perhydrol solution. The autopsy concluded that the immediate cause of death was an acute cardiopulmonary failure due to the toxic effects of intravenously administered hydrogen peroxide. This conclusion was established after the toxicological testing of the evidence and biological material secured during the patient’s treatment and autopsy. Products containing DMSO and perhydrol are not included in the lists of medicinal/therapeutical forms and preparations and thus are not authorised for marketing in Poland. In the case of perhydrol, apart from the topical use of diluted preparations for washing and cleansing wounds, no data on therapeutic use exist in the available scientific literature. Furthermore, “DMSO and perhydrol therapy” cannot even be considered a placebo effect, as both are toxic compounds which could, at most, cause poisoning symptoms rather than improve health