Oral Liquid Formulation of Levothyroxine Is Stable in Breakfast Beverages and May Improve Thyroid Patient Compliance

Patients on treatment with levothyroxine (T4) are informed to take this drug in the morning, at least 30 min before having breakfast. A significant decrease of T4 absorption was reported, in fact, when T4 solid formulations are taken with food or coffee. According to preliminary clinical study reports, administration of T4 oral solution appears to be less sensitive to the effect of breakfast beverages on oral bioavailability. In the present study, stability of T4 oral solution added to breakfast beverages was investigated. A 1 mL ampoule of single-dose Tirosint® oral solution (IBSA Farmaceutici Italia, Lodi, Italy) was poured into defined volumes of milk, tea, coffee, and coffee with milk warmed at 50 °C, as well as in orange juice at room temperature. Samples were sequentially collected up to 20 min and analyzed by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The results of the study demonstrated that T4 is stable in all beverages after 20 min incubation. Demonstration of T4 stability is a prerequisite for a thorough evaluation of the effect of breakfast beverages on the bioavailability of T4 given as oral solution and for a better understanding of the reasons underlying a decreased T4 bioavailability administered as solid formulations

Detection of cocaine on euro banknotes; Development of a practical approach for the interpretation of suspect cases.

The presence of traces of narcotics, particularly cocaine, on banknotes in circulation is a known and widespread fact in all countries. While linked to consumption and trafficking (primary contamination), their spread is due to direct contact with other banknotes during machine counting and cash financial transactions. The mere detection of traces of cocaine on a sample of banknotes is therefore not sufficient evidence to establish the banknote's illegal origin. Increasing levels of contamination are recorded close to (in terms of both place and time) the first direct contact with the substance. The analysis must thus be able to demonstrate that the concentration of narcotics on the banknotes is significantly higher (statistically) in terms of value and frequency than would be expected from background noise alone. Even in that event, however, this evidence has to be substantiated with additional confirmations linking banknotes to the person and this latter to drug trafficking and/or dealing. In general, an in-depth and systematic analysis of all seized banknotes to search for traces of narcotics is not only prohibitive in terms of cost, but also unnecessary. If the sampling procedure is respected, the Swiss Federal Supreme Court actually recognizes IMS (ion mobility spectrometry) as a lawful method for checking the degree of banknote contamination, as well as all the statistical conclusions that can be drawn from it. In special cases, the prosecutor may require confirmation of IMS results by a laboratory test (liquid/gas chromatography-mass spectrometry). Using a non-destructive sampling procedure (suction on swabs) we determined the presence of cocaine on 978 circulating euro banknotes, randomly collected at 5 swiss customs offices, with IMS and LC-MS/MS in order to establish a normal (background) contamination level. A significant proportion (46.4%) of the euro banknotes analysed by LC-MS/MS had cocaine concentrations above the quantification limit (1 ng/swab). However, the extent of contamination is a determining factor: 94.6% of the banknotes in circulation have cocaine concentrations equal to or less than 10 ng/swab and only 3.4% have cocaine concentrations above 20 ng/swab. By comparison, only 27.3% and 13.4% respectively of the seized banknotes (2 real cases) had cocaine concentrations equal to or less than 10 ng/swab, but 63.5% and 86.7% respectively had cocaine concentrations above 20 ng/swab. We also describe a Komolgorov-Smirnov test model used to determine the presence of an "abnormal" level of contamination relative to the reference banknotes (banknotes in circulation or background noise) effectively and within realistic practical and theoretical frameworks. This model provides a quantifiable and statistically significant result that not only simplifies data interpretation, but also facilitates admissibility as forensic evidence in proceedings. When applied to the sized banknotes using both IMS and LC-MS/MS data, we obtain fully consistent and sounding conclusions

Biomarkers, matrices and analytical methods targeting human exposure to chemicals selected for a European human biomonitoring initiative

The major purpose of human biomonitoring is the mapping and assessment of human exposure to chemicals. The European initiative HBM4EU has prioritized seven substance groups and two metals relevant for human exposure: Phthalates and substitutes (1,2-cyclohexane dicarboxylic acid diisononyl ester, DINCH), bisphenols, per- and polyfluoroalkyl substances (PFASs), halogenated and organophosphorous flame retardants (HFRs and OPFRs), polycyclic aromatic hydrocarbons (PAHs), arylamines, cadmium and chromium. As a first step towards comparable European-wide data, the most suitable biomarkers, human matrices and analytical methods for each substance group or metal were selected from the scientific literature, based on a set of selection criteria. The biomarkers included parent compounds of PFASs and HFRs in serum, of bisphenols and arylamines in urine, metabolites of phthalates, DINCH, OPFRs and PAHs in urine as well as metals in blood and urine, with a preference to measure Cr in erythrocytes representing Cr (VI) exposure. High performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was the method of choice for bisphenols, PFASs, the HFR hexabromocyclododecane (HBCDD), phenolic HFRs as well as the metabolites of phthalates, DINCH, OPFRs and PAHs in urine. Gas chromatographic (GC) methods were selected for the remaining compounds, e.g. GC-low resolution MS with electron capture negative ionization (ECNI) for HFRs. Both GC–MS and LC-MS/MS were suitable for arylamines. New developments towards increased applications of GC–MS/MS may offer alternatives to GC–MS or LC-MS/MS approaches, e.g. for bisphenols. The metals were best determined by inductively coupled plasma (ICP)-MS, with the particular challenge of avoiding interferences in the Cd determination in urine. The evaluation process revealed research needs towards higher sensitivity and non-invasive sampling as well as a need for more stringent quality assurance/quality control applications and assessments.This study was part of the HBM4EU project receiving funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032