Development of UPLC–MS/MS method for studying the pharmacokinetic interactions of pexidartinib with antifungal drugs in rats

Shi, Lu; Jiang, Zheli; Zhang, Bowen; Tang, Congrong; Xu, Ren-ai

doi:10.1016/j.jpba.2020.113386

Cited by 13 publications

(5 citation statements)

References 9 publications

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“…Pentachlorophenol is also a metabolite of other organochlorines, including the pesticide hexachlorobenzene(73) which has been associated with dairy consumption in Sweden. (74) Another common co-exposure (Group B, Figure S24 ) included homologues of polyethyleneglycol (Level 2, ICC 0-0.31, 36-100% DF), which are approved by the US Food and Drug Administration for dermal, oral and intravenous pharmaceutical applications,(75) and have been detected in environmental samples,(76,77) but not in human samples previously. Group C co-exposures ( Figure S23 ) included sodium lauryl sulfate (ICC 0.09, 45% DF, confirmed Level 1), strongly correlated with tetradecyl sulfate (Level 2; ICC 0.07, 36% DF; r 0.92, p < 0.001, n = 276, Figure 4B ) and lauryl diethanolamide (Level 2; ICC 0.01, 32% DF; r 0.66, p < 0.001, n = 276), all of which are ingredients in household cleaning and personal care products, such as detergents, shampoos, liquid soap and cosmetics.…”

Section: Resultsmentioning

confidence: 99%

Longitudinal Exposomics in a Multiomic Wellness Cohort Reveals Distinctive and Dynamic Environmental Chemical Mixtures in Blood

Sdougkou,

Papazian,

Bonnefille

et al. 2024

Preprint

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Chemical exposomes can now be comprehensively measured in human blood, but robust application of chemical exposomics in cohort studies requires knowledge of the longitudinal stability and interindividual variability of exogenous molecular profiles. Here we applied chemical exposomics to plasma of 46 adults, each sampled six times over two years in a multiomic wellness cohort. New chemicals were discovered, distinctive co-exposure patterns were observed, and intra-class correlation coefficients (ICC) for 519 confidently annotated substances are reported to support study design. Longitudinal stability of the chemical exposome (mean ICC 0.30) was significantly lower than the proteome, metabolome, lipidome or microbiome, and must be measured more frequently than other molecular profiles in health studies. Mixed-effects models nevertheless revealed significant associations between testosterone and perfluoroalkyl substances, and significant time-trends for low and high stability exposures alike. Complex exposome data structures were visualized and explored, demonstrating great potential for longitudinal exposomics in precision health research.

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Section: Resultsmentioning

confidence: 99%

Longitudinal Exposomics in a Multiomic Wellness Cohort Reveals Distinctive and Dynamic Environmental Chemical Mixtures in Blood

Sdougkou,

Papazian,

Bonnefille

et al. 2024

Preprint

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“…The LOD and LOQ of CRI in the cell culture medium are 2.44 and 7.39 μg/mL, this may be because of the serious overlap between the unknown interfering substance and CRI in the cell culture medium, and the response intensity of CRI is relatively low in a unit concentration. According to published literature, the concentration of the nine TKIs in people's plasma is around 298–5000 ng/ml [22–24]. The LOQ obtained by ATLD–MCR can basically meet the need of quantitation, having the potential for clinical application.…”

Section: Resultsmentioning

confidence: 99%

Simultaneous determination of nine tyrosine kinase inhibitors in three complex biological matrices by using high‐performance liquid chromatography–diode array detection combined with a second‐order calibration method

Wang

Chang

Wei

et al. 2021

J of Separation Science

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An intelligent chemometric second‐order calibration method called alternating trilinear decomposition‐ assisted multivariate curve resolution combined with high‐performance liquid chromatography–diode array detection was used for the simultaneous quantification of nine tyrosine kinase inhibitors in three complex biological systems. The method allows simultaneous quantification of the components in different biological matrices without the need for cumbersome pre‐treatment steps, complex elution conditions, and complete peak separation. Even with the varying time shift, severe peak overlap, and various unknown interferences, the proposed method can extract pure chromatographic and spectroscopic information for each analyte, while providing accurate qualitative and quantitative results of nine common tyrosine kinase inhibitors in three different biological matrices. All the drugs were eluted in 7 min. The results showed that the nine drugs in each matrix showed good linearity (r > 0.984) in the calibration range with a root mean square error of calibration less than 0.9 μg/mL. The average spiked recoveries of the target analytes were all in the range of 83.4–110.0%, with standard deviations less than 9.0%. Finally, the classical method was used to validate the proposed method. In comparison to the traditional method, the proposed strategy is accuracy, simultaneous, and interference‐free.

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“…Te most frequent adverse events associated with PXD, a small molecule TKI, were hair hypopigmentation or transient transaminase elevation, and serious or permanent adverse events, especially cholestatic hepatotoxicity, were rare [21]. DDIs in the PXD were reported when combined with the sedative-hypnotic drug midazolam, the cardiac glycoside analog digoxin, the proton pump inhibitor omeprazole [19], and the antifungal drugs fuconazole and itraconazole [22]. Te PXD carried a risk of fatal hepatic injury, so prompt hepatoprotective therapy was essential.…”

Section: Ddismentioning

confidence: 99%

Exploring the Effect of Compound Glycyrrhizin and Silybinin on the Metabolism of Pexidartinib in Rats Based on CYP3A4 and CYP2C9

Su,

Wei,

Cheng

et al. 2023

Advances in Pharmacological and Pharmaceutical Sciences

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Pexidartinib offered a new therapeutic option for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) who were refractory to surgical treatment and had severe morbidity or functional limitations. Meanwhile, the metabolism of pexidartinib was mainly mediated through the oxidation of cytochrome P450 (CYP) 3A and glucuronidation by uridine glucuronosyltransferase (UGT) 1A4 and attention shall be paid to CYP450-based drug-drug interactions during therapeutic dosing. This study aimed to examine the changes in the pharmacokinetics of pexidartinib by silymarin and compound glycyrrhizin on pexidartinib in vivo in rats by high-performance liquid chromatography (HPLC)-UV approach and to detect its expression in CYP3A4 and CYP2C9 using the western blot. The findings of chromatography experiments revealed that silybinin as well as compound glycyrrhizin increased the exposure of pexidartinib in rats and had a significant inhibitory effect on the metabolism of pexidartinib. The results of immunoblotting assays suggested that silybinin as well as compound glycyrrhizin inhibited the protein expression of CYP3A4 and CYP2C9 in rats. Therefore, the combination of pexidartinib with silybinin and compound glycyrrhizin should be monitored to avoid clinical adverse effects.

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Development of UPLC–MS/MS method for studying the pharmacokinetic interactions of pexidartinib with antifungal drugs in rats

Cited by 13 publications

References 9 publications

Longitudinal Exposomics in a Multiomic Wellness Cohort Reveals Distinctive and Dynamic Environmental Chemical Mixtures in Blood

Longitudinal Exposomics in a Multiomic Wellness Cohort Reveals Distinctive and Dynamic Environmental Chemical Mixtures in Blood

Simultaneous determination of nine tyrosine kinase inhibitors in three complex biological matrices by using high‐performance liquid chromatography–diode array detection combined with a second‐order calibration method

Exploring the Effect of Compound Glycyrrhizin and Silybinin on the Metabolism of Pexidartinib in Rats Based on CYP3A4 and CYP2C9

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