Effect of three herbicides namely 2,4-D, metsulfuron-methyl and glyphosate was evaluated on fish mortality and water quality in relation to control of aquatic form of alligator weed (Alternanthera philoxeroides; Family, Amaranthaceae). All herbicides caused fish mortality and affected water quality after application, but it was highest in 2,4-D treated tanks followed by glyphosate and metsulfuronmethyl. Herbicide did not cause fish mortality at 1 DAA (days after application) but it caused at 7 DAA and increased corresponding to increase in concentration and days. Fish mortality was recorded lowest in herbicides treated tanks that were having only water but no weeds. Significantly higher fish mortality occurred in 2,4-D treated tanks having weeds. This reflected that fish mortality was more due to decaying of weeds, which decreased dissolved oxygen drastically in the water tanks. Herbicides did not affect fish development because growth and weight of fish was highest in water tanks treated with herbicides having no weeds. All the herbicides significantly decreased pH in treated tanks than control at 0 and 1 DAA, however, it was resumed towards normalisation in due course. The decrease in pH was least in the tanks having weeds and treated with metsulfuron-methyl followed by glyphosate and 2,4-D. Further, decrease in pH was less in water tanks having no weeds than having weeds. All the herbicides significantly decreased the dissolved oxygen (DO) at 0 day in water tanks with and without weeds except metsulfuron-methyl in the tanks having no weeds. Decrease in DO was more prominent in 2,4-D treated tanks followed by glyphosate and metsulfuron-methyl. Dissolved oxygen was least affected in tanks having no weeds.
A simple, sensitive, fast and inexpensive method was developed using solid-phase extraction (SPE), ultrasound and QuEChERS method with Ultra Fast Liquid Chromatography (UFLC) for trace level determination of imidacloprid in vegetables (Cabbage and Spinach) and Soil. The method was validated using Cabbage, Spinach and soil samples spiked with imidacloprid at different concentration levels (LOQ 0.01, 10 x LOQ 0.10 and 50 x LOQ 0.50 µg/g). Average recoveries (using each concentration 5 replicates) ranged from 89.39 to 99.5%, with relative standard deviations less than 2.15%, calibration solutions concentration used were in the range 0.005 -1.0 µg/mL and limit of detection (LOD) and limit of quantification (LOQ) were 0.005 µg/mL and 0.01 µg/mL, respectively.
Background
Nephrotoxicity is a dose-limiting factor for polymyxin B (PMB), a last-line therapy for MDR Gram-negative bacterial infections. The majority of the filtered PMB undergoes extensive tubular reabsorption leading to significant accumulation of the drug in tubular cells, causing renal tubular damage. We have previously reported that VRP-034, a novel PMB formulation, attenuates this damage (Roy et al.1). The objective of this study was to characterize the pharmacokinetics (PK) and renal accumulation of VRP-034 versus marketed PMB.
Materials and methods
A total of 19 Sprague-Dawley rats were used in the study. For PK evaluation, 10 rats were administered a single subcutaneous dose (6 mg/kg) of either VRP-034 or marketed PMB. Serial plasma samples were collected up to 24 h and assayed for major PMB components (PMB B1, B1-I, B2) using a validated LC-tandem MS method. PK parameters were calculated using noncompartmental analysis. For evaluating renal deposition, nine rats (n = 3 each group) were administered VRP-034 or marketed PMB at a dose of 6 mg/kg/8 h for 48 h or normal saline (control). After 48 h, rats were euthanized and kidneys were excised by making a midline incision, washed with saline, homogenized in 1:9 w/v 0.1 M phosphate buffer (pH 7.4) and the homogenate was used for determining PMB concentration. All values are expressed as mean ± SEM.
Results
The plasma pharmacokinetic parameters for both VRP-034 and marketed PMB were found similar [AUC0–24: 54.3 ± 4.7 μg/mL·h versus 51.5 ± 1.6 μg/mL·h; Cmax: 4.73 ± 0.6 μg/mL versus 5.02 ± 0.5 μg/mL; T½: 5.95 ± 0.5 h versus 5.6 ± 0.3 h]. In the renal deposition study, a 40% reduction (P<0.05) in renal deposition of PMB was found in VRP-034 treated rat kidneys compared with marketed PMB group after 48 h of treatment.
Conclusions
The results highlight that while the plasma PK parameters remained unchanged, a marked reduction in PMB renal deposition was observed in VRP-034 group and likely explains the previous reports of attenuated PMB-induced kidney injury with VRP-034.
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