Development and validation of analytical method for the determination of radotinib in human plasma using liquid chromatography-tandem mass spectrometry

Seo, Hyo-Bum; Cho, Seung Il; Yoon, Young‐Ran

doi:10.12793/tcp.2017.25.4.183

Cited by 3 publications

(3 citation statements)

References 6 publications

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“…35,46 There are studies using similar and different molecules as ISs for Aml 30,31,35 as well as studies using Aml as an IS. [42][43][44][45][46]49 The drugs commonly used as ISs might have either positive or negative effects. The fact that they are easy to obtain, are well-defined, and are included in a great amount of research could be the positive side; however, for the sample to contain that IS would be the negative side.…”

Section: Resultsmentioning

confidence: 99%

“…When the literature was reviewed, it was found that different chemical structured molecules were also used instead of the novel similar molecules, and even multiple molecule scans that could be considered as ISs of each other within the same study were used, too. , There are studies using similar and different molecules as ISs for Aml ,, as well as studies using Aml as an IS. − , …”

Section: Resultsmentioning

confidence: 99%

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Determination of Tryptophan and Kynurenine by LC–MS/MS by Using Amlodipine as an Internal Standard

Eser

Özkan

Dinçel

2020

J. Am. Soc. Mass Spectrom.

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Tryptophan is an essential amino acid that plays an important role in cell metabolism, and kynurenine is its main metabolic pathway. By using ultra-high-performance liquid chromatography coupled to electrospray ionization triple–quadrupole mass spectrometry, tryptophan and kynurenine were determined using amlodipine as an internal standard. The analysis was carried out on an ACE-C18 (4.6 mm × 50 mm, 5 μm) reversed-phase analytical column using the gradient elution mode. For quantitative determination, amlodipine was used as an internal standard. Detection was performed using multiple reaction monitoring in electrospray ionization mode at m/z 205.1 → 117.7 and 187.9 for tryptophan, m/z 209.1 → 146 and 93.9 for kynurenine, and m/z 409.2 → 294.1 for the internal standard. Good linearity of the analyte to internal standard peak area ratios was seen in the concentration range 1.25–4000 ng/mL for tryptophan and 0.5–1600 ng/mL for kynurenine. The method showed excellent linearity with regression coefficients of 0.99 for kynurenine and 0.996 for tryptophan. The limits of quantification were 0.55 ng/mL for tryptophan and 0.47 ng/mL for kynurenine. The % RSD for all analytes ranged from 0.3 to 3.4% for intraday and 0.4 to 8.9% for interday experiments. A simple LC–MS/MS method has been developed and validated for measuring Kyn and Trp by using an affordable and more easily available internal standard, which is amlodipine.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Determination of Tryptophan and Kynurenine by LC–MS/MS by Using Amlodipine as an Internal Standard

Eser

Özkan

Dinçel

2020

J. Am. Soc. Mass Spectrom.

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“…4 and Fig S3). Vitamins that regulate metabolism in living organisms act as catalysts for enzymatic reactions, or as coenzymes that carry chemical groups between them [ 26 ]. In particular, vitamins play a very important role in the metabolic pathways of mitochondrial respiration and energy production, which maintain essential vital activities in vivo.…”

Section: Discussionmentioning

confidence: 99%

Radotinib attenuates TGFβ -mediated pulmonary fibrosis in vitro and in vivo: exploring the potential of drug repurposing

Baek¹,

Kwon

Jeon

et al. 2022

BMC Pharmacol Toxicol

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Background Tyrosine kinase (TK) plays a crucial role in the pathogenesis of idiopathic pulmonary fibrosis. Here, we aimed to investigate whether radotinib (Rb) could inhibit pulmonary fibrosis by inhibiting TK in vitro and in vivo. Methods The antifibrotic effects of Rb in transforming growth factor-β (TGF-β)1-stimulated A549 cells were determined using real-time polymerase chain reaction, western blotting, and immunocytochemistry assays. Rb inhibition of bleomycin-induced lung fibrosis in Sprague Dawley (SD) rats was determined by histopathological and immunohistochemical analyses. Rb-interfering metabolites were analyzed using LC-MS/MS. Results Rb concentrations of up to 1000 nM did not affect the viability of A549 cells, but Rb (30 nM) significantly reduced expression of TGF-β1 (10 ng/mL)-induced ECM factors, such as Snail, Twist, and F-actin. Rb also regulated TGF-β1-overexpressed signal cascades, such as fibronectin and α-smooth muscle actin. Furthermore, Rb attenuated the phosphorylation of Smad2 and phosphorylation of kinases, such as, extracellular signal-regulated kinase, and protein kinase B. In the inhibitory test against bleomycin (5 mg/kg)-induced lung fibrosis, the Rb (30 mg/kg/daily)-treated group showed a half-pulmonary fibrosis region compared to the positive control group. In addition, Rb significantly reduced collagen type I and fibronectin expression in the bleomycin-induced fibrotic region of SD rats. Further, the identified metabolite pantothenic acid was not altered by Rb. Conclusion Taken together, these results indicate that Rb inhibits TGF-β1-induced pulmonary fibrosis both in vitro and in vivo. These findings suggest that Rb may be an effective treatment for pulmonary fibrosis-related disorders and idiopathic pulmonary fibrosis.

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Differential vascular endothelial cell toxicity of established and novel BCR-ABL tyrosine kinase inhibitors

Wang,

Travers,

Farrell

et al. 2023

PLoS ONE

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BCR-ABL tyrosine kinase inhibitors (TKIs) have dramatically improved survival in Philadelphia chromosome-positive leukemias. Newer BCR-ABL TKIs provide superior cancer outcomes but with increased risk of acute arterial thrombosis, which further increases in patients with cardiovascular comorbidities and mitigates survival benefits compared to imatinib. Recent studies implicate endothelial cell (EC) damage in this toxicity by unknown mechanisms with few side-by-side comparisons of multiple TKIs and with no available data on endothelial impact of recently approved TKIs or novels TKIs being tested in clinical trials. To characterize BCR-ABL TKI induced EC dysfunction we exposed primary human umbilical vein ECs in 2D and 3D culture to clinically relevant concentrations of seven BCR-ABL TKIs and quantified their impact on EC scratch-wound healing, viability, inflammation, and permeability mechanisms. Dasatinib, ponatinib, and nilotinib, the TKIs associated with thrombosis in patients, all significantly impaired EC wound healing, survival, and proliferation compared to imatinib, but only dasatinib and ponatinib impaired cell migration and only nilotinib enhanced EC necrosis. Dasatinib and ponatinib increased leukocyte adhesion to ECs with upregulation of adhesion molecule expression in ECs (ICAM1, VCAM1, and P-selectin) and leukocytes (PSGL1). Dasatinib increased permeability and impaired cell junctional integrity in human engineered microvessels, consistent with its unique association with pleural effusions. Of the new agents, bafetinib decreased EC viability and increased microvessel permeability while asciminib and radotinib did not impact any EC function tested. In summary, the vasculotoxic TKIs (dasatinib, ponatinib, nilotinib) cause EC toxicity but with mechanistic differences, supporting the potential need for drug-specific vasculoprotective strategies. Asciminib and radotinib do not induce EC toxicity at clinically relevant concentrations suggesting a better safety profile.

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Development and validation of analytical method for the determination of radotinib in human plasma using liquid chromatography-tandem mass spectrometry

Cited by 3 publications

References 6 publications

Determination of Tryptophan and Kynurenine by LC–MS/MS by Using Amlodipine as an Internal Standard

Determination of Tryptophan and Kynurenine by LC–MS/MS by Using Amlodipine as an Internal Standard

Radotinib attenuates TGFβ -mediated pulmonary fibrosis in vitro and in vivo: exploring the potential of drug repurposing

Differential vascular endothelial cell toxicity of established and novel BCR-ABL tyrosine kinase inhibitors

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