Absorption, Distribution and Excretion
The jugular-vein cannulated rats (five males and five females per group) were killed at 48 hr after dosing. The bile-duct cannulated rats (three males per group) were killed at 24 hr after dosing. Blood samples were taken from the jugular cannula at 0.25, 0.5, 0.75, 1, 1.5, 3, 6, 12, 24 and 48 hr. Urine, feces and bile were collected regularly throughout the study. Peak plasma radioactivity (Cmax) was detected at approximately 0.5 hr (2-3 ug equiv./g) at 10 mg/kg bw and approximately 1.5 hr (80-90 mg equiv./g) at 500 mg/kg bw. ... There were no significant differences between the repeat-dose and single-dose groups. The elimination of radioactivity from blood followed a similar pattern. The area-under-the-curve (AUC) of the plasma versus time graph for the elimination of radiolabel in plasma (0-48 hr) was 22.3, 27.3 and 922 ug equiv. hr/g in males and 30.4, 29.6 and 963 ug equiv. hr/g in females after treatments with a single radiolabelled dose, a single radiolabelled dose after repeated dosing and 500 mg/kg bw (14)C-quinoxyfen respectively.
By 24 hr after dosing, 68-85% of the administered radioactivity had been recovered in the feces and urine, indicating rapid elimination from the body. After 48 hr, 90-96% of the administered (14)C-quinoline ring-labelled quinoxyfen was recovered in the urine, feces, cage wash and tissues. The feces represented the major route of elimination as 68-78% of the administered dose was eliminated via this route in 48 hr, while 13-20% was eliminated in the urine. Urinary half-lives ranged from 6 to 10 hr. The tissues and carcass accounted for 1-7%, contents of the gastrointestinal tract for < 3% and final cage wash for < 1% of the administered dose. There were no sex differences in the distribution of radiolabel. Repeated administration of quinoxyfen did not affect the distribution of the radio-labelled dose.
The distribution of radiolabel in organs and tissues (percentage of administered dose/g tissue) 48 hr after treatment with a single dose of quinoline ring-labelled quinoxyfen at 10 mg/kg bw showed that the highest amounts of radiolabel were present in perirenal fat (0.12 in males and 0.35 females) > ovaries (0.07) > liver (0.027 in males and 0.045 in females) and kidneys (0.014 in males and 0.033 in females). Significant levels were found in the skin. Similar amounts were obtained after repeated dosing and a similar pattern after the higher dose of 500 mg/kg bw. There were no data on tissue levels at times approximating to the plasma Cmax.
Comparison of the relative concentrations in bile and urine of intact and bile-duct cannulated rats indicated that enterohepatic recirculation is extensive with quinoxyfen at a dose of 10 mg/kg bw. In bile-duct cannulated rats, there was a marked difference in the amount of radiolabel in the feces of rats at 10 mg/kg bw (14.3%) compared with those at 500 mg/kg bw (57.3%) and in the amount of radiolabel in the bile of rats at 10 mg/kg bw (54.4%) compared with those at 500 mg/kg bw (21.4%). These findings indicated that absorption of quinoxyfen at a dose of 500 mg/kg bw dose was saturated.
For more Absorption, Distribution and Excretion (Complete) data for Quinoxyfen (7 total), please visit the HSDB record page.

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Metabolism / Metabolites
Groups of 5 Fischer 344 rats/sex were given a single 10 or 500 mg/kg oral dose of quinoline ring-labeled (14)C- quinoxyfen (XDE-795, >99% radiochemically pure, specific active 28.5 mCi/mmole), or 14 daily oral doses of 10 mg/kg of non-radiolabelled quinoxyfen (XDE-795, 99% pure) followed by a single 10 mg/kg oral dose of (14)C- quinoxyfen. Additional groups of 3 male bile duct cannulated rats received a single dose of 10 or 500 mg/kg quinoline ring-labelled (14)C- quinoxyfen and were sacrificed 24 hrs later. One rat/sex/group received 10 mg/kg of either phenyl ring (98.5% radiochemically pure, specific active 27.8 mCi/mmole) or quinoline ring-labelled (14)C- quinoxyfen for metabolite analysis. ... Major metabolites identified in the urine were derived from cleavage of the diaryl-ether linkage quinoxyfen resulting in the formation of acid-labile conjugates of 4-fluorophenol (4-FP) and 5, 7-dichloro-4-hydroxyquinoline (DCHQ), and lesser quantities of free DCHQ and 4-FP. Glucuronide and/or sulfate conjugates of two isomers of fluorophenyl ring-hydroxy- quinoxyfen were detected in the bile. Parent quinoxyfen and free forms of the same two isomers of fluorophenyl ring-hydroxy- quinoxyfen as seen in the bile were detected in feces. No substantive differences in the metabolism and disposition of quinoxyfen between sexes or single and repeated administration.
HPLC separation of pooled 0-12 hr urine samples from the preliminary study in rats given phenyl-ring-labelled (14)C-quinoxyfen produced eight peaks that were designated P1-P7 and P10. Peak P5 was the major urinary fraction in the unhydrolyzed urine sample (80% and 77.4% in the male and female respectively) followed by P3 (7.9% and 9.5%), P1 (4.2% and 4.7%) and P6 (3.1% and 3.0%). The remaining peaks contained less than 3% of the urinary radiolabel. Acid hydrolysis of the urine produced a significant change in the HPLC profile. The major fraction in unhydrolyzed urine was reduced to only 2.4% of the urine fraction; instead, P8 (not detectable in the unhydrolyzed sample) was the major fraction (73.6%). This suggested that P5 might be a conjugate of P8. The P8 fraction was found to co-elute with the standard for 4-fluorophenol. The remaining minor peaks after acid hydrolysis were P3 (11.7%), P9 (7.1%) and P1 (5.2%), but these metabolites were not identified. The standards used were 4-fluorophenol, 2-hydroxy-quinoxyfen and parent quinoxyfen. Parent quinoxyfen and 2-hydroxy-quinoxyfen retention times did not correspond to that of any of the HPLC urinary fractions. Fecal metabolites from phenyl-(14)C quinoxyfen showed a similar pattern to those from quinoline-(14)C quinoxyfen.
HPLC separation of pooled urine samples from groups receiving quinoline-(14)C quinoxyfen ... before and after acid hydrolysis produced up to 16 radiolabelled peaks that were designated Q1-Q16. In male rats receiving a single dose at 10 mg/kg bw, eight peaks were identified in unhydrolyzed urine: Q3, Q4, Q7, Q8, Q9, Q11, Q12 and Q13. In females rats receiving a single dose at 10 mg/kg bw, four additional peaks were detected: Q2, Q5, Q10 and Q15 (repeated-dose only). For the males and females at 500 mg/kg bw, the peaks in the radiochromatogram of pooled 0-12 hr urine samples were Q7, Q8, Q9, Q10 (female only), Q11, Q12 and Q13. The major peaks were Q11 (13-33%), Q8 (13-24%), Q9 (9-24%), Q12 (10-18%), Q13 (6-15%), Q7 (4-11%) and Q4 (< 13%). The only clearly identified urinary metabolite was 5,7 dichloro-4-hydroxyquinoline (DCHQ), which was found to co-elute with peak Q13. Acid hydrolysis resulted in a two- to four-times increase in Q13 (24-65%). In the males rats receiving a single dose at 10 mg/kg bw, increases were observed in peaks Q3, Q6 and Q14, while peaks Q1 and Q2 were increased after acid hydrolysis. In rats receiving a single dose at 500 mg/kg bw, peak Q14 was increased in males. Concomitantly, peaks Q4, Q5, Q7, Q8 and Q10 were observed to disappear from the respective radiochromatograms, while Q3 and Q9 were markedly reduced. Enzyme hydrolysis did not affect the metabolite profile.
HPLC separation of bile samples (taken at various time-points, 0-24 hr) from male rats receiving quinoline ring-labelled quinoxyfen at 10 mg/kg bw or 500 mg/kg bw produced six peaks (B2-B7). Peaks B6 and B7 constituted 20-66% and 26-59% of biliary excretion at various time-points. For the 10 mg/kg bw rats, the amount of radiolabel in the peaks at various time-points were B2 6-15%; B5 4-15%; B3 and B4 < 5%. Only peaks B6 and B7 were detected in the samples from rats at 500 mg/kg bw, but this was attributed to the higher detection limits required by the investigating laboratory. Additional peaks B1, B8, B9 and B10 were detected after enzyme hydrolysis. Peak B7 was noted to disappear with the appearance of peak B10 (approximately 25%) suggesting that B7 is the glucuronide or sulfatase of B10. Acid hydrolysis of the bile samples from rats at 10 or 500 mg/kg bw resulted in an increase in B6 by 20% of the biliary radioactivity compared with the control. Peaks B1, B8 and B9 appeared in the sample from rats at 10 mg/kg bw, but were not detected at 500 mg/kg bw. B10 eluted with quinoxyfen, but MS showed that the key ions were 16 mass units greater than the corresponding fragment ions from quinoxyfen. It was concluded that two metabolites associated with peak B10 were isomers of fluorophenyl-ring hydroxylated quinoxyfen.
For more Metabolism/Metabolites (Complete) data for Quinoxyfen (7 total), please visit the HSDB record page.

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Biological Half-Life
The jugular-vein cannulated rats (five males and five females per group) were killed at 48 hr after dosing. The bile-duct cannulated rats (three males per group) were killed at 24 hr after dosing. Blood samples were taken from the jugular cannula at 0.25, 0.5, 0.75, 1, 1.5, 3, 6, 12, 24 and 48 hr. Urine, feces and bile were collected regularly throughout the study. ... The elimination of plasma radioactivity followed a biphasic pattern with half-lives for the rapid and slow phases for the dose at 10 mg/kg bw of < 1 hr and 15-19 hr respectively, and 2-3 hr and 18-22 hr for the dose at 500 mg/kg bw. There were no significant differences between the repeat-dose and single-dose groups. ...

Non-Human Toxicity Values
LD50 Rabbit dermal >2000 mg/kg
LC50 Rat inhalation > 3.38 mg/L (mass median aerodynamic diameter 3.6 um) /Duration not specified/
LD50 Rat oral >5000 mg/kg

Quinoxyfen is a member of the class of quinolines carrying two chloro substituents at positions 5 and 7 together with a 4-fluorophenoxy substituent at position 4. A fungicide used mainly to control powdery mildew in cereals. It has a role as an antifungal agrochemical. It is an aromatic ether, a member of quinolines, an organochlorine compound and a member of monofluorobenzenes.
Quinoxyfen is a fungicide used mainly to control Erysiphe graminis - powdery mildew in cereals. It functions systemically with protective properties, translocates and inhibits appressoria development stopping infections.

C15H8CL2FNO

308.13

306.996

124495-18-7

Quinoxyfen-d4

3391107

Crystals from heptane
Off-white solid

1.4±0.1 g/cm3

423.2±45.0 °C at 760 mmHg

105-106°

209.7±28.7 °C

0.0±1.0 mmHg at 25°C

1.648

6.29

0

3

2

20

325

0

C1=C(C=CC(=C1)OC2=CC=NC3=CC(=CC(=C32)Cl)Cl)F

WRPIRSINYZBGPK-UHFFFAOYSA-N

InChI=1S/C15H8Cl2FNO/c16-9-7-12(17)15-13(8-9)19-6-5-14(15)20-11-3-1-10(18)2-4-11/h1-8H

5,7-dichloro-4-(4-fluorophenoxy)quinoline

DE-795 QuinoxyfenDE795Legend DE 795

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~16.67 mg/mL (~54.10 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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