Comparative Pharmacokinetic Study of Forchlorfenuron in Adult and Juvenile Rats

Li, Ping; Xu, Bingyong; Zhou, Qian; Yang, Hong; Sun, Qian; Wang, Jincheng; Zhu, Difeng

doi:10.3390/molecules26144276

Cited by 8 publications

(5 citation statements)

References 22 publications

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“…Guidance for Industry [11]. The following performance metrics of the method were examined: specificity, lower limit of detection, lower limit of quantification (LLOQ), linearity, precision and accuracy, recovery, matrix effect (ME), and so on [12].…”

Section: Methods Validationmentioning

confidence: 99%

Development and Validation of an Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Quantitative Determination of N-((3S,4S)-4-(3,4-Difluorophenyl)piperidin-3-yl)-2-fluoro-4-(1-methyl-1H-pyrazol-5-yl)benzamide in Dog Plasma

Dong

Zuo

et al. 2021

Applied Sciences

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The PI3K/AKT/MTOR signalling pathway plays an important role in the growth and proliferation of tumour cells. N-((3S,4S)-4-(3,4-Difluorophenyl)piperidin-3-yl)-2-fluoro-4-(1-methyl-1H-pyrazol-5-yl)benzamide (Hu7691) is a new-generation selective AKT inhibitor developed at Zhejiang University. In this study, we developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the measurement of Hu7691 in dog plasma. Plasma was precipitated with acetonitrile and then separated on a trifunctionally bonded alkyl column. Excellent separation efficiency and selectivity were achieved by adjusting the mobile phase ratio, with a total running time of only 5 min. The linear dynamic range of the calibration curve was 5–1000 ng/mL. The method was fully validated, and all performance metrics met the criteria. The validated method was used for the pharmacokinetic monitoring and bioavailability assessment of Hu7691 in dogs. The results showed that the area under the curve and peak plasma concentration of Hu7691 increased with increasing dose (oral 5, 10, 20 mg/kg, intravenous 10 mg/kg), and oral bioavailabilities were 86.7%, 50.8%, and 50.5%, respectively, indicating a high bioavailability of Hu7691 in dogs. This provides a test basis for the clinical application of the compound.

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Section: Methods Validationmentioning

confidence: 99%

Development and Validation of an Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Quantitative Determination of N-((3S,4S)-4-(3,4-Difluorophenyl)piperidin-3-yl)-2-fluoro-4-(1-methyl-1H-pyrazol-5-yl)benzamide in Dog Plasma

Dong

Zuo

et al. 2021

Applied Sciences

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“…In addition, a study by Gong et al reported that FCF induced cardiac morphology deformation, cardiac contractile dysfunction, and erythrocyte reduction in zebrafish [17,19]. In a more recent study evaluating the potential safety risks of FCF on juvenile rats, Ping et al emphasized the risks of FCF exposure in children after finding that juvenile rats exhibited reduced plasma clearance (CLz) when compared to adult rats [20]. With human populations facing increased exposure to FCF residues through the consumption of fruits and vegetables, these bioaccumulations have also been shown to cause cyto-genotoxicity in human lymphocytes [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Fungal-Mediated Biotransformation of the Plant Growth Regulator Forchlorfenuron by Cunninghamella elegans

Moreno,

Valdez

et al. 2024

Metabolites

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The synthetic cytokinin forchlorfenuron (FCF), while seemingly presenting relatively low toxicity for mammalian organisms, has been the subject of renewed scrutiny in the past few years due to its increasing use in fruit crops and potential for bioaccumulation. Despite many toxicological properties of FCF being known, little research has been conducted on the toxicological effects of its secondary metabolites. Given this critical gap in the existing literature, understanding the formation of relevant FCF secondary metabolites and their association with mammalian metabolism is essential. To investigate the formation of FCF metabolites in sufficient quantities for toxicological studies, a panel of four fungi were screened for their ability to catalyze the biotransformation of FCF. Of the organisms screened, Cunninghamella elegans (ATCC 9245), a filamentous fungus, was found to convert FCF to 4-hydroxyphenyl-forchlorfenuron, the major FCF secondary metabolite identified in mammals, after 26 days. Following the optimization of biotransformation conditions using a solid support system, media screening, and inoculation with a solid pre-formed fungal mass of C. elegans, this conversion time was significantly reduced to 7 days—representing a 73% reduction in total reaction time as deduced from the biotransformation products and confirmed by LC-MS, NMR spectroscopic data, as well as a comparison with synthetically prepared metabolites. Our study provides the first report of the metabolism of FCF by C. elegans. These findings suggest that C. elegans can produce FCF secondary metabolites consistent with those produced via mammalian metabolism and could be used as a more efficient, cost-effective, and ethical alternative for producing those metabolites in useful quantities for toxicological studies.

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“…Furthermore, Zhu et al [3] stated that CPPU could promote estradiol secretion and adversely affect prepubertal female rats. Furthermore, Ping et al [7] reported that CPPU had more potent effects on juvenile rats than adult rats in a pharmacokinetic experiment. Therefore, it is speculated that CPPU is potentially harmful to adolescent health.…”

Section: Introductionmentioning

confidence: 99%

Production of a Monoclonal Antibody for the Detection of Forchlorfenuron: Application in an Indirect Enzyme-Linked Immunosorbent Assay and Immunochromatographic Strip

Lei

El‐Aty

et al. 2023

Biosensors

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In this study, a monoclonal antibody (mAb) specific to forchlorfenuron (CPPU) with high sensitivity and specificity was produced and designated (9G9). To detect CPPU in cucumber samples, an indirect enzyme-linked immunosorbent assay (ic-ELISA) and a colloidal gold nanobead immunochromatographic test strip (CGN-ICTS) were established using 9G9. The half-maximal inhibitory concentration (IC50) and the LOD for the developed ic-ELISA were determined to be 0.19 ng/mL and 0.04 ng/mL in the sample dilution buffer, respectively. The results indicate that the sensitivity of the antibodies prepared in this study (9G9 mAb) was higher than those reported in the previous literature. On the other hand, in order to achieve rapid and accurate detection of CPPU, CGN-ICTS is indispensable. The IC50 and the LOD for the CGN-ICTS were determined to be 27 ng/mL and 6.1 ng/mL. The average recoveries of the CGN-ICTS ranged from 68 to 82%. The CGN-ICTS and ic-ELISA quantitative results were all confirmed by liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) with 84–92% recoveries, which indicated the methods developed herein are appropriate for detecting CPPU in cucumber. The CGN-ICTS method is capable of both qualitative and semiquantitative analysis of CPPU, which makes it a suitable alternative complex instrument method for on-site detection of CPPU in cucumber samples since it does not require specialized equipment.

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Comparative Pharmacokinetic Study of Forchlorfenuron in Adult and Juvenile Rats

Cited by 8 publications

References 22 publications

Development and Validation of an Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Quantitative Determination of N-((3S,4S)-4-(3,4-Difluorophenyl)piperidin-3-yl)-2-fluoro-4-(1-methyl-1H-pyrazol-5-yl)benzamide in Dog Plasma

Development and Validation of an Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Quantitative Determination of N-((3S,4S)-4-(3,4-Difluorophenyl)piperidin-3-yl)-2-fluoro-4-(1-methyl-1H-pyrazol-5-yl)benzamide in Dog Plasma

Fungal-Mediated Biotransformation of the Plant Growth Regulator Forchlorfenuron by Cunninghamella elegans

Production of a Monoclonal Antibody for the Detection of Forchlorfenuron: Application in an Indirect Enzyme-Linked Immunosorbent Assay and Immunochromatographic Strip

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