2-(4-methylphenoxy)-N-(1H-pyrazol-3-yl)-N-[(thiophen-2-yl)methyl]acetamide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Objective of study:

other: stability

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The purpose of this study was to determine the relative stability of test item in human plasma as compared to other species in order to determine the suitability of the rat as a species for toxicology studies.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(4-methylphenoxy)-N-(1H-pyrazol-3-yl)-N-[(thiophen-2-yl)methyl]acetamide

EC Number:

815-961-9

Cas Number:

1374760-95-8

Molecular formula:

C17H17N3O2S

IUPAC Name:

2-(4-methylphenoxy)-N-(1H-pyrazol-3-yl)-N-[(thiophen-2-yl)methyl]acetamide

Test material form:

not specified

Details on test material:

No data

Specific details on test material used for the study:

- Storage condition of test material: Stored at approximately 25 °C away from direct sunlight until the day of the experiment and/or analysis

Radiolabelling:

no

Results and discussion

Any other information on results incl. tables

The test item (750 ng/mL) was incubated with dog, human, minipig, monkey, rabbit, or rat plasma at 37°Cfor 24 hours. Peak area of the test item and S8551 (internal standard) as well as the ratio of peak area of test item/S8551, and normalized data in the various species are summarized in Table 1.

The test item was rapidly hydrolyzed in rat plasma with only 3.8% remaining at the 15 minute time point. In contrast, the test item was very stable in human, dog, and pig plasma with 90.0%, 110.4%, and 91.7%, respectively, remaining at the 24 hour time point. The test item was less stable in either monkey or rabbit plasma with 36.7% and 20.1%, respectively, remaining at the 24 hour time point. The results indicate that the plasma stability of the test item in humans is most similar to either dog or Gottingen pig.

Applicant's summary and conclusion

Conclusions:

The test item was rapidly hydrolyzed in rat plasma with only 3.8% remaining at the 15 minute time point. In contrast, the test item was very stable in human, dog, and pig plasma with 90.0%, 110.4%, and 91.7%, respectively, remaining at the 24 hour time point. The test item was less stable in either monkey or rabbit plasma with 36.7% and 20.1%, respectively, remaining at the 24 hour time point. The results indicate that the plasma stability of the test item in humans is most similar to either dog or Gottingen pig.

Executive summary:

A study was conducted to determine the relative stability of the test item in human plasma as compared to other species in order to assess the suitability of the rat as a species for toxicology studies.

The test item (750 ng/mL) was incubated with human, rat, dog, rabbit, monkey, or Gottingen pig plasma at 37 °C for 24 hours. Duplicate aliquots (50 µL) were taken at 0, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0, and 24 hours and diluted into acetonitrile (150 µL) containing an internal standard (S8551). The samples were centrifuged to separate the precipitated proteins from the supernatant. The supernatant was analyzed by LC-MS/MS using an API 3200 QTrap equipped with an Agilent 1100 HPLC system in order to determine the percent of the test item remaining at the various time points. All data were normalized by ratio of peak area (test item/S8551) at the 0 hour time point.

 

The test item was rapidly hydrolyzed in rat plasma with only 3.8% remaining at the 15 minute time point. In contrast, the test item was very stable in human, dog, and pig plasma with 90.0%, 110.4%, and 91.7%, respectively, remaining at the 24 hour time point. The test item was less stable in either monkey or rabbit plasma with 36.7% and 20.1%, respectively, remaining at the 24 hour time point. The results indicate that the plasma stability of the test item in humans is most similar to either dog or Gottingen pig.