Mutagenicity assessment of two potential impurities in preparations of 5-amino-2,4,6 triiodoisophthalic acid, a key intermediate in the synthesis of the iodinated contrast agent iopamidol.

5-Aminoisophthalic acid and 5-nitroisophthalic acid (5-NIPA) are potential impurities in preparations of 5-amino-2,4,6-triiodoisophthalic acid, which is a key intermediate in the synthesis of the iodinated contrast agent iopamidol. We have studied their mutagenicity in silico (quantitative structure-activity relationships, QSAR) and by the bacterial reverse mutation assay (Ames test). First, the compounds were screened with the tools Derek Nexus™ and Leadscope®. Both compounds were flagged as potentially mutagenic (class 3 under ICH M7). However, contrary to the in silico prediction, neither chemical was mutagenic in the Ames test (plate incorporation method) with or without S9 metabolic activation.

Development and validation of a UHPLC-HRMS-QTOF method for the detection of 132 New Psychoactive Substances and synthetic opioids, including fentanyl, in Dried Blood Spots.

Dried Blood Spots (DBS) represents a promising micro-sampling technique in the field of forensic toxicology to carry out minimally invasive blood sample collection. In DBS, cheap, fast and easy sampling is combined with effortless store and transport. These properties aimed us to develop and validate a quick and easy procedure for the detection of a large and diverse range of emerging and alarming New Psychoactive Substances (NPS). A drop of whole blood sample was collected on a DBS card and dried for 3 h, from which a total of 132 analytes (including NPS, synthetic opioids NSO and metabolites) plus 13 deuterated internal standards could be extracted using 500 µL of a methanol/acetonitrile mixture (3:1, v/v) and subsequently separated and identified by means of ultra-high-performance liquid-chromatography (UHPLC) coupled to high resolution mass spectrometry (HRMS). The extraction efficiency proved to be reproducible with yields ranging from 30% to 100% depending on the different classes of drugs. Trueness, repeatability, and intermediate precision fulfilled acceptance criteria for almost all synthetic opioids, cathinones and hallucinogens (bias and CV% below ±20%); in particular, the aggregate inter-day trueness data showed extremely limited deviation from the expected concentrations (-10% < bias% < +10%) for 114 target analytes out of 132. The calculated limits of detection ranged from 1.3 to 6.3 ng/mL, consistently exceeding the values experimentally tested. Moderate ion suppression was observed for most analytes, partly caused by blood fortification itself. Good stability of the target analytes at -20 °C, 4 °C, and 35 °C on DBS cards after drying was observed, even for long periods of time. Optimal storage condition appeared to be at 4 °C resulting in virtually no drugs degradation for up to 40 days. The novel analytical method based on DBS sampling, verified on venous whole blood real samples previously tested positive with our routine procedure, conveys remarkable potential in analytical toxicology, clinical analysis, and doping control.