Pralidoxime chloride 1g powder for solution for injection vials

Pralidoxime chloride, a highly hydrophilic antidote, cannot be effectively separated by reverse-phase high-performance liquid chromatography (RP-HPLC), unless the mobile-phase composition is varied. However, the use of ion-pairing reagents for pralidoxime separation is hindered by the persistent contamination of the stationary phase or chromatography system inside the HPLC system. Thus, this study aimed to develop a simple, rapid, and robust method based on RP-HPLC to determine pralidoxime chloride in antidote autoinjectors using a chaotropic salt as the mobile-phase additive. The use of UV detection at 270 nm allowed for the simultaneous detection of pralidoxime chloride and the internal standard, pyridine-2-aldoxime. The addition of chaotropic salts (NaPF6, NaBF4, and NaClO4) and an ionic liquid ([EMIM]PF6) increased the retention time of pralidoxime chloride. Among them, NaPF6 exhibited the highest capacity factor in the reverse-phase C18 column. Increasing the salt concentration increased the capacity factor and the number of theoretical plates. Analytical method validation was performed to assess the linearity, accuracy, precision, recovery, and repeatability, according to the Ministry of Food and Drug Safety guidelines. Additionally, this newly developed method exhibits an adequate separation capability, making it a potential substitute for the current method employed in the United States/Korean Pharmacopoeia, and it ensures the necessary durability to maintain the robustness and reliability of the analytical system.

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In this work, a flexible electrochemical sensor was developed for the detection of organophosphorus pesticides (OPs). To fabricate the sensor, graphene was generated in situ by laser-induced graphene (LIG) technology on a flexible substrate of polyimide (PI) film to form a three-electrode array, and pralidoxime (PAM) chloride was used as the probe molecule. CeO2 was used to modify the working electrode to improve the sensitivity of the sensor because of its electrocatalytic effect on the oxidation of PAM, and the Ag/AgCl reference electrode was prepared by the drop coating method. The effects of the laser power, laser scanning speed, and CeO2 modification on the electrochemical properties of the sensor were studied in detail. The results prove that the sensor has good repeatability, stability, and anti-interference ability, and it shows an excellent linear response in the chlorpyrifos concentration range from 1.4 × 10−8 M to 1.12 × 10−7 M with the detection limit of 7.01 × 10−10 M.

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Purpose: We synthesized folic acid-conjugated Fe3O4/Au-pralidoxime chloride Nanoparticles (Fe2O3/Au@PAM NPs) for use as dual-modal contrast agents for Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) in the diagnosis of breast cancer. Materials and Methods: Fe2O3/Au@PAM NPs labeled or not to folic acid were synthesized and analyzed by dynamic light scattering, transmission electron microscopy, and vibrating sample magnetometry. The ability of these NPs to create image contrast was also investigated in silico and in vitro (in MCF-7 breast cancer cells and A549 lung cancer cells) with CT and MRI. Results: Dynamic light scattering and transmission electron microscopy revealed that the Fe2O3/Au@PAM NPs were nearly spherical. The average diameter of Fe2O3/Au NPs increased from 11.6 nm to 98 nm after folic acid conjugation. The saturation magnetization values of Fe2O3/Au@PAM NPs with and without folic acid conjugation were 25.56 and 32.6 emu/g, respectively. Conjugation of folic acid to NPs greatly improved their uptake by cancer cells. The additional coating of NPs with FA reduced the T2 relaxation time and signal intensity for MRI. Folic acid-labeled MCF-7 cells had a radiodensity measurement of 208 Hunsfield Units (HU) compared to 95 HU for A549 cells. For breast cancer cells, NPs labeled with folic acid significantly improved the X-ray absorption coefficient as a sign of active cellular uptake compared to NPs without labeling. Conclusion: Folic acid-labeled Fe2O3/Au@PAM NPs can serve as dual CT/MRI contrast agents and improve the sensitivities of both modalities for the detection of cancer cells.

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Background: Organophosphate (OP) poisoning is a potentially life-threatening condition that predominantly affects the nervous system. Acute kidney injury (AKI), particularly intrinsic acute tubular necrosis (ATN), is a rare but serious complication. Acute respiratory distress syndrome (ARDS) may further complicate severe intoxication. Case presentation: A 41-year-old female intentionally ingested 48 % soluble chlorpyrifos. She developed vomiting, abdominal pain, decreased level of consciousness, oliguria, and generalized edema. On examination, she was hypotensive, tachycardic, tachypneic, and hypoxic. Laboratory investigations revealed metabolic acidosis, elevated serum creatinine (4.1 mg/dL), blood urea nitrogen (47 mg/dL), electrolyte imbalances, reduced serum cholinesterase level, and a fractional excretion of sodium (FENa) of 3 %, consistent with intrinsic renal injury. Imaging demonstrated pulmonary edema and bilaterally enlarged kidneys. She was treated with intravenous fluids, atropine infusion (0.02 mg/kg/h), pralidoxime (30 mg/kg bolus followed by 8 mg/kg/h infusion), intermittent hemodialysis for AKI, supplemental oxygen, and mechanical ventilation for ARDS. Over 84 hours, urine output improved, renal function recovered, and respiratory distress resolved. She was discharged after one week with plan for psychiatric evaluation and monthly ambulatory nephrology follow-up. Conclusion: This case highlighted a rare presentation of intrinsic ATN complicated by ARDS following OP poisoning. Early recognition and intensive supportive management of renal and respiratory complications are essential. Clinicians should consider direct OP-induced nephrotoxicity in severe poisoning to optimize outcomes.

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Organophosphate poisoning can precipitate acute atrial fibrillation even in previously healthy individuals. This first documented case from Pakistan of Malathion-induced atrial fibrillation emphasizes the need for early recognition, continuous cardiac monitoring, prompt atropine and pralidoxime therapy, electrolyte correction, and timely cardioversion to ensure full recovery.

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This case report presents a rare instance of combined dichlorvos (organophosphate) and brodifacoum (rodenticide) poisoning. By analyzing the clinical presentation and therapeutic course, we aim to provide insights into the challenges and management strategies associated with multi-agent toxic exposures. A 73-year-old male with a history of hypertension and depression was admitted after ingesting approximately 150 mL of dichlorvos and 10 mL of brodifacoum. He underwent 18 days of comprehensive treatment, including gastric decontamination with induced emesis and activated charcoal, administration of specific antidotes (a total of 1189 mg atropine, 21.8 g pralidoxime iodide, and 660 mg vitamin K1), and extracorporeal detoxification via hemoperfusion and hemofiltration. Supportive care involved infection control, nutritional supplementation, and monitoring of coagulation and electrolyte status. The patient developed early complications, including hematemesis, epistaxis, and persistent coagulopathy, as well as transient alterations in consciousness and cholinesterase levels below 200 U/L. With prompt and aggressive intervention, his clinical condition gradually stabilized, and he was discharged in good condition. Follow-up revealed coagulopathy, with deep vein thrombosis requiring oral anticoagulation. Combined organophosphate and rodenticide poisoning presents a complex toxicological scenario, characterized by overlapping and synergistic effects on the nervous and coagulation systems. Cholinesterase levels below 200 U/L may serve as a critical marker of severity in patients without pre-existing liver disease. Hemoperfusion effectively facilitates toxin clearance, though adjustments to pralidoxime iodide dosing may be warranted during extracorporeal therapy. Following blood purification therapy, no toxin was detected in the patient’s plasma, and long-term coagulation abnormalities associated with super warfarin exposure were not observed in this case. Additionally, electrolyte disturbances and myocardial biomarkers such as myoglobin and troponin require close observation, as they may reflect ongoing systemic injury. While this case highlights several clinical considerations, further studies are needed to establish standardized protocols for managing multi-toxin exposures of this nature.

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The French Poison Centers database is a tool of choice for the analysis of poisoning cases requiring the administration of an antidote although not all uses are systematically reported. This national retrospective study aims to report trends of use of antidotes in France over a 7-year period from 2015 to 2021. A total of 25,289 cases of poisoning required the administration of an antidote, among which 46.7% were moderate to severe. While 77.1% of poisonings progressed toward recovery, the observed mortality rate was 1.7%. The 3 most frequently used antidotes according to data from Poison Centers were N-acetylcysteine (n = 13,555 [53.6%]), flumazenil (n = 3102 [12.3%]) and naloxone (n = 1740 [6.9%]) reflecting the most common types of poisoning involving acetaminophen, benzodiazepines, and opioids. The observed use of methylthioninium chloride, hydroxocobalamin, cyanocobalamin and DOAC reversal agents increased, both in terms of absolute numbers and proportions, revealing new behaviors leading to poisoning, such as nitrous oxide consumption. Conversely, the observed use of ethanol-based therapy, L-carnitine, and dantrolene decreased over time, reflecting both current medical practices and shifts in guidelines. This study provides a novel insight into the typology (circumstances, severity, development) of poisonings requiring an antidote, as well as the description of the causative agents.

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Lethal organophosphate (OP) exposure leads to status epilepticus (SE), which, despite standard-of-care (SOC) therapy, is associated with acute mortality and long-term morbidities. Neuronal injury and inflammation are reported following OP-SE, and drugs targeted at these processes have produced beneficial outcomes. Verapamil (VPM) is a calcium-channel blocker used as an antihypertensive drug and has been shown to exhibit neuroprotective and anti-inflammatory actions in experimental models of CNS injuries. Here, we investigated the feasibility of an adjunctive intramuscular (i.m.) VPM therapy in OP Diisopropyl Fluorophosphate (DFP)-induced SE. We also investigated the safety and toxicity of i.m. VPM and compared its pharmacokinetic (PK) profile to oral (p.o.) administration. Rats were injected with DFP (4 mg/kg, s.c.). One minute later, SOC treatment consisting of atropine (0.5 mg/kg, i.m.) and pralidoxime chloride (2-PAM; 25 mg/kg, i.m.) were administered, and at 1-hour post-SE, midazolam (1.78 mg/kg, i.m.) was given. Rats that met the behavioral SE severity criteria (Racine 4-5) were randomized into two treatment groups: those receiving saline (SAL) or VPM (10 mg/kg, i.m. bid, 3 days). Histological analysis was conducted to assess neuronal injury and injection-site pathology. In a separate group of rats, PK studies were conducted on blood and brain homogenates treated once with saline or VPM (10 mg/kg, p.o. or i.m.). Our data demonstrated that following DFP-SE, i.m. VPM achieved higher blood and brain levels and exhibited a favorable PK profile compared to p.o. route. VPM therapy did not cause significant muscle pathology and produced a robust neuroprotective response. Neuroinflammatory markers and long-term behavioral outcomes were not included in this study. Our studies provide evidence that the i.m. route is an effective method for delivering VPM following SE, producing significant neuroprotective outcomes compared to treatment with the standard-of-care alone in OP-SE.

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Animal research continues to serve a critical role in the testing and development of medical countermeasures. The Göttingen minipig, developed for laboratory research, may provide many benefits for addressing research questions within chemical defense. Targeted development of the Göttingen minipig model could reduce reliance upon non-human primates, and improve study design, statistical power, and throughput to advance medical countermeasures for regulatory approval and fielding. In this vein, we completed foundational pharmacokinetics and physiological safety studies of intramuscularly administered atropine sulfate, pralidoxime chloride (2-PAM), and diazepam across a broad range of doses (1–6 autoinjector equivalent) using adult male Göttingen minipigs (n=11; n=4–8/study) surgically implanted with vascular access ports and telemetric devices to monitor cardiovascular, respiratory, arterial pressure, and temperature signals. Pharmacokinetic data were orderly and the concentration maximum mirrored available human data at comparably scaled doses clearly for atropine, moderately for 2-PAM, and poorly for diazepam. Time to peak concentration approximated 2, 7, and 20 min for atropine, 2-PAM, and diazepam, respectively, and the elimination half-life of these drugs approximated 2 hr (atropine), 3 hr (2-PAM), and 8 hr (diazepam). Atropine sulfate dose-dependently increased the magnitude and duration of tachycardia and decreased the PR and ST intervals (consistent with findings obtained from other species). Mild hypothermia was observed at the highest diazepam dose. Göttingen minipigs appear to provide a ready and appropriate large animal alternative to non-human primates, and further development and evaluation of novel nerve agent medical countermeasures and treatment strategies in this model are justified. • Pharmacokinetics were evaluated in conscious, unrestrained adult male minipigs. • Doctrinal nerve agent countermeasures were studied across a large range of doses. • Physiological measures were also recorded for general safety assessment. • Orderly pharmacokinetic data and expected/minor physiological changes were observed. • The Göttingen minipig may provide a suitable large animal model for pharmacology.

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