Absorption, Distribution and Excretion
Following a single or multiple oral dose of 5 mg/kg Pyraflufen-ethyl, it is rapidly absorbed and excreted within 96 hours (plasma half-life of 3 to 3.5 hours). However, absorption saturates at doses up to 500 mg/kg, and the Cmax values do not reflect a 100-fold dose difference (2.7 to 2.8 Fg eq/g in the low-dose group and 100 to 107 Fg eq-hr/g in the high-dose group). Following a single or multiple oral dose of low-dose (5 mg/kg) Pyraflufen-ethyl, urinary excretion accounts for 27% to 33% of the administered radioactivity, indicating that multiple dosing regimens do not affect the absorption/excretion process. After a single 500 mg/kg dose, urinary excretion decreases to only 5% to 7%. In all treatment groups, the remaining radioactive material is excreted in feces. Bile excretion analysis following a single 5 mg/kg dose showed that 36% of the administered dose appeared in bile. Based on excretion data, the overall bioavailability of the low-dose group was approximately 56%. Due to the lack of bile excretion data for the high-dose group, its bioavailability could not be definitively assessed. No sex difference was observed in excretion patterns. However, plasma and blood clearance were faster in women than in men, as evidenced by the plasma/blood radioactivity time course and higher AUC values in men (32.3 vs 18.4 Fg eq-hr/g for the low-dose group and 2,738 vs 1,401 Fg eq-hr/g for the high-dose group). Radioactivity concentrations showed that at 96 hours post-administration, radioactivity concentrations in all tissues were at or near the limit of detection (generally <0.01 Fg eq/g and never exceeding 0.02 Fg eq/g). Therefore, Pyraflufen-ethyl and its metabolites did not appear to have significant retention. Tissue load data after compound administration did not reveal specific targets other than the liver and kidneys (tissues associated with the absorption and elimination of orally administered exogenous substances). [EPA 40 CFR Part 180]

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Metabolism/Metabolites
Five Sprague-Dawley rats of each sex were administered 5 mg/kg of [phenyl-U-14C]ET-751 via a single gavage. Each animal was immediately transferred to a glass metabolic cage after administration. Urine and feces were collected every 24 hours for 96 hours. Metabolites in urine and feces were evaluated using high-performance liquid chromatography (HPLC) and two-dimensional thin-layer chromatography (2-D TLC). Metabolites were identified in urine and feces. Similar to [pyrazole-5-14C]ET-751, the hypothesized metabolic pathway is ester hydrolysis and N-demethylation of the pyrazole ring at position 1, followed by hydrolysis of the ether bond at position 5 of the benzene ring to phenol, and methylation to methoxy group. Twenty male Sprague-Dawley rats were administered unlabeled ET-751 technology via gavage for 14 consecutive days at a dose of 5 mg/kg/day. On day 15, they were given a single gavage dose of [pyrazole-5-14C] ET-751 at a dose of 5 mg/kg. Metabolites in urine, feces, plasma, and gastrointestinal contents were identified using high-performance liquid chromatography (HPLC). After 96 hours, the total values in urine and feces were 26.66% and 64.44%, respectively. …After 96 hours, the concentrations in all samples were below or equal to the limits of detection. Metabolites in urine, feces, and plasma were identified…The hypothesized metabolic pathway is ester hydrolysis and N-demethylation at the 1-position of the pyrazole ring, and hydrolysis of the ether bond at the 5-position of the benzene ring to generate phenol followed by methylation to generate a methoxy group. Six male Sprague-Dawley rats were administered a single oral gavage dose of 5 mg/kg of [Pyrazole-5-14C] ET-751 via bile duct cannulation. Metabolites were identified using high-performance liquid chromatography (HPLC). Within 48 hours of administration, 17.90% (feces), 19.66% (urine), and 36.09% (bile) of the radioactive material were excreted. After 48 hours, 13.86% of the radioactive material was present in the gastrointestinal contents, and 2.86% remained in the gastrointestinal tract. The estimated oral absorption rate was 55.75% (total urine and bile). Metabolites were identified in urine, feces, the gastrointestinal tract, and gastrointestinal contents. The hypothesized metabolic pathway involves ester hydrolysis and N-demethylation at the 1-position of the pyrazole ring, and hydrolysis of the ether bond at the 5-position of the benzene ring to generate a phenolic hydroxyl group. Five male and five female Sprague-Dawley rats in each group were injected with 5 or 500 mg/kg of [pyrazole-5-14C]ET-751 and sacrificed at 3, 6, 9, 24, 96, or 168 hours later, respectively. ...Metabolites were identified in urine, plasma, and feces...The hypothesized metabolic pathway is ester hydrolysis and N-demethylation at the 1-position of the pyrazole ring, and hydrolysis of the ether bond at the 5-position of the benzene ring to generate phenol, followed by methylation to generate a methoxy group.

[1]. Parthenium hysterophorus L. control in response to pyraflufen-ethyl application. Crop Protection, Volume 57, March 2014, Pages 35-37.

Pyraflufen-ethyl is an ethyl ester formed by the condensation of the carboxyl group of pyrflufenicol and ethanol. As a prodrug of pyrflufenicol, it is used to control broadleaf and grassy weeds in various crops. It has multiple functions, including acting as an EC 1.3.3.4 (protoporphyrinogen oxidase) inhibitor, a prodrug, and an agrochemical. It belongs to the pyrazole, biaryl, ethyl ester, aromatic ether, monochlorobenzene, and monofluorobenzene classes of compounds. Its function is similar to that of pyrflufenicol. Pyraflufen-ethyl is a selective contact herbicide used to control broadleaf and grassy weeds in crops.

C15H13N2O4F3CL2

413.17592

383.989

129630-19-9

182951

Light yellow to light brown solid powder

1.6±0.1 g/cm3

468.9±40.0 °C at 760 mmHg

126-127 °C

237.4±27.3 °C

0.0±1.2 mmHg at 25°C

1.575

2.73

0

8

8

26

480

0

APTZNLHMIGJTEW-UHFFFAOYSA-N

InChI=1S/C15H13Cl2F3N2O4/c1-3-24-11(23)6-25-10-4-7(9(18)5-8(10)16)13-12(17)14(22(2)21-13)26-15(19)20/h4-5,15H,3,6H2,1-2H3

ethyl 2-[2-chloro-5-[4-chloro-5-(difluoromethoxy)-1-methylpyrazol-3-yl]-4-fluorophenoxy]acetate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~242.03 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 2: ≥ 1.25 mg/mL (3.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)