LC-MS/MS methods for the determination of 30 quaternary ammonium compounds including benzalkonium and paraquat in human serum and urine.

Benzalkyldimethylammonium (or benzalkonium; BACs), alkyltrimethylammonium (ATMACs), and dialkyldimethylammonium compounds (DDACs) have been widely used for over six decades as disinfectants, especially during the COVID-19 pandemic. Here we describe methods for the determination of 7 BACs, 6 ATMACs, 6 DDACs, 8 BAC metabolites, and the structurally similar quaternary ammonium compound (QAC) herbicides diquat, paraquat, and difenzoquat in human serum and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The methods were optimized using isotopically labelled internal standards and solid-phase extraction with weak cation-exchange cartridges. We separated diquat and paraquat chromatographically using a mixed-mode LC column, and BACs, ATMACs, DDACs, difenzoquat, and BAC metabolites using reversed-phase (C8 and C18) LC columns. Method limits of detection (MLODs) and quantification (MLOQs) were 0.002-0.42 and 0.006-1.40 ng/mL, respectively. Recoveries of all analytes fortified at 1, 5, and 20 ng/mL concentrations in serum and urine matrices were 61-129%, with standard deviations of 0-20%. Repeated analysis of similarly fortified serum and urine samples yielded intra-day and inter-day variations of 0.22-17.4% and 0.35-17.3%, respectively. Matrix effects for analytes spiked into serum and urine matrices ranged from -27% to 15.4%. Analysis of real urine and serum samples revealed the presence of several QACs in human serum. Although no parent BACs were found in urine, we detected, for the first time, several ω-hydroxy and ω-carboxylic acid metabolites of BACs at average concentrations in the range of 0.05-0.35 ng/mL. The developed method is suitable for application in large-scale biomonitoring of human exposure to QACs and their metabolites in human serum and urine.

A review: The phytochemistry, pharmacology, and pharmacokinetics of Curcumae Longae Rhizoma (Turmeric)

Curcumae Longae Rhizoma (CLR) is the rhizome of Curcuma longa L. Pharmacological studies show that CLR can be used to treat cervical cancer, lung cancer, lupus nephritis, and other conditions. In this paper, we review botany, traditional application, phytochemistry, pharmacological activity, and pharmacokinetics of CLR. The literature from 1981 to date was entirely collected from online databases, such as Web of Science, Google Scholar, China Academic Journals full-text database (CNKI), Wiley, Springer, PubMed, and ScienceDirect. The data were also obtained from ancient books, theses and dissertations, and Flora Reipublicae Popularis Sinicae. There are a total of 275 compounds that have been isolated from CLR, including phenolic compounds, volatile oils, and others. The therapeutic effect of turmeric has been expanded from breaking blood and activating qi in the traditional sense to antitumor, anti-inflammatory, antioxidation, neuroprotection, antibacterial, hypolipidemic effects, and other benefits. However, the active ingredients and mechanisms of action related to relieving disease remain ill defined, which requires more in-depth research and verification at a clinical level.

Paraquat ingestion and COVID-19 infection: deadly double hit

Objective: To describe two cases of intentional paraquat ingestion as self-harm in patients with COVID-19 infection. Methods: We retrospectively analysed poisoning cases (accidental and suicidal), admitted to a dedicated COVID-19 care facility at our institute. As a protocol, all patients coming to our emergency department were reverse transcriptase-PCR tested for novel coronavirus disease 2019 (nCOVID-19) before being admitted to a high dependency unit (HDU) intensive care unit (ICU). If they tested positive for COVID they were transferred to a dedicated COVID care facility. These patients were treated according to the protocol developed for poisoned patients. All patients were followed until discharge or death. We describe the details of 2 patients with intentional paraquat ingestion. Results: We received nine patients at our dedicated COVID care facility created at our institute during the pandemic. Of these 9, 2 patients had ingested paraquat and presented with acute respiratory distress syndrome (ARDS). Both patients were in the third decade of life and the economic crisis due to the pandemic was the trigger for the ingestion of paraquat. Both had ingested a significant amount of commercially available paraquat. They had significant acute kidney and liver injury at presentation and required dialysis. Haemoperfusion was not performed as the charcoal filters were not available. The clinical picture and chest X-rays were similar to the findings observed in severe COVID-19 patients. Since patients were hypoxic at presentation, monoclonal antibodies were not indicated and were not administered. Both patients were given dexamethasone (6mg daily), as per the “COVID treatment protocol”. We did not administer pulse doses of methylprednisolone or cyclophosphamide due to concerns over exacerbating COVID infection. One of the patients developed significant oesophageal ulceration leading to massive haematemesis. Both developed spontaneous pneumomediastinum and succumbed to their illness after an average stay of 8 days in the HDU. Conclusion: During the pandemic, paraquat ingestion for selfharm with COVID-19 infection poses a challenge to treating physicians. Since the clinical picture of ARDS, is similar to severe COVID infection, the management with immunosuppressive agents becomes difficult.