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Article ; Online: The Pharmacokinetic Interaction of Tirabrutinib with Voriconazole, Itraconazole, and Fluconazole in SD Rats by UPLC-MS/MS.

Xia, Mengming / Liu, Ya-Nan / Chen, Jie / Xu, Ren-Ai / Dai, Gexin

2024

Abstract: Background: Tirabrutinib is an orally effective, approved, and highly selective second-generation Bruton's tyrosine kinase (BTK) inhibitor for the treatment of recurrent or refractory primary central nervous system lymphoma (PCNSL).: Objective: This ... ...

Abstract	Background: Tirabrutinib is an orally effective, approved, and highly selective second-generation Bruton's tyrosine kinase (BTK) inhibitor for the treatment of recurrent or refractory primary central nervous system lymphoma (PCNSL). Objective: This study aimed to develop an ultra-high performance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS) method for the determination of tirabrutinib concentration in rat plasma, where zanubrutinib was used as an internal standard (IS). This method was also applied to study whether tirabrutinib would interact with voriconazole, itraconazole, and fluconazole in rats, providing a reference value for clinical medication guidance. Methods: In the current study, the organic solvent protein precipitation method was used to treat plasma samples, which is simple and reproducible. Tirabrutinib (m/z 455.32 → 320.21) and zanubrutinib (m/z 472.13 → 455.04) were separated on a Waters Acquity BEH C18 column (2.1 × 50 mm, 1.7 μm) and detected by multiple reaction monitoring (MRM) in positive ionization mode. Results: The method showed good linearity in the range of 5-3000 ng/mL for tirabrutinib with the lower limit of quantification (LLOQ) of 5 ng/mL. The recovery and matrix effects were 85.7-91.0% and 102.0-113.3%, respectively. The accuracy, precision, stability, and carry-over effect were also acceptable. The method could also be used for determining the pharmacokinetic interaction of tirabrutinib in rats. The results showed AUC0→∞ of tirabrutinib to be increased by 139.3% and 83.9% in the presence of voriconazole and fluconazole, respectively, while itraconazole had little effect. Conclusion: It is necessary to monitor the concentration of tirabrutinib in patients when it is combined with voriconazole and fluconazole to achieve a better therapeutic effect and reduce the risk of adverse reaction. Further research should be conducted in the future.
Language	English
Publishing date	2024-01-10
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/0109298673268883231108062655
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Article ; Online: Effects of myricetin and quercetin on ticagrelor metabolism and the underlying mechanism.

Wang, Jing / Hu, Yingying / Li, Qingqing / Liu, Ya-Nan / Lin, Jingjing / Xu, Ren-Ai

Chemico-biological interactions

2024 Volume 392, Page(s) 110924

Abstract: The aim of this study was to investigate the potential drug-drug interactions (DDIs) between ticagrelor and other drugs as well as their underlying mechanisms. Rat liver microsome (RLM) reaction system was used to screen potential DDIs in vitro, and ... ...

Abstract	The aim of this study was to investigate the potential drug-drug interactions (DDIs) between ticagrelor and other drugs as well as their underlying mechanisms. Rat liver microsome (RLM) reaction system was used to screen potential DDIs in vitro, and ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to detect the levels of ticagrelor and AR-C124910XX, the main metabolite of ticagrelor. A total of 68 drugs were screened, 11 of which inhibited the production of AR-C124910XX to 20% or less, especially two flavonoids (myricetin and quercetin). The half-maximal inhibitory concentration (IC
MeSH term(s)	Humans ; Rats ; Animals ; Ticagrelor/pharmacology ; Ticagrelor/metabolism ; Quercetin/pharmacology ; Chromatography, Liquid/methods ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry/methods ; Flavonoids/pharmacology ; Flavonoids/metabolism ; Microsomes, Liver/metabolism
Chemical Substances	Ticagrelor (GLH0314RVC) ; myricetin (76XC01FTOJ) ; Quercetin (9IKM0I5T1E) ; Flavonoids
Language	English
Publishing date	2024-02-23
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	218799-1
ISSN	1872-7786 ; 0009-2797
ISSN (online)	1872-7786
ISSN	0009-2797
DOI	10.1016/j.cbi.2024.110924
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Article ; Online: Simultaneous determination of iguratimod and its metabolite in rat plasma using a UPLC-MS/MS method: Application for drug-drug interaction.

Shi, Lu / Hu, Jinyu / Wu, Hualu / Shen, Yuxin / Chen, Xiaohai / Weng, Qinghua / Xu, Ren-Ai / Tang, Congrong

Journal of pharmaceutical and biomedical analysis

2024 Volume 243, Page(s) 116079

Abstract: This aim of the work was to establish an acceptable sensitive assay based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for quantitatively analyzing the plasma concentrations of iguratimod (IGR) and its metabolite M2 in ...

Abstract	This aim of the work was to establish an acceptable sensitive assay based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for quantitatively analyzing the plasma concentrations of iguratimod (IGR) and its metabolite M2 in rats, and to further investigate the effect of fluconazole on the pharmacokinetics of IGR and M2. The mobile phase consisted of acetonitrile and water with 0.1% formic acid, was used to separate IGR, M2 and internal standard (IS) fedratinib on a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with the flow rate of 0.4 mL/min. Positive ion mode and multiple reaction monitoring (MRM) were used to construct the quantitative analysis. The calibration standard of IGR and M2 covered 2-10000 and 1-1000 ng/mL respectively, with the lower limit of quantification (LLOQ) as 2 ng/mL and 1 ng/mL respectively. In addition, selectivity, recovery, accuracy, precision, matrix effect and stability of the method validation program were well accepted in this work. Subsequently, this approach was used to assess the effect of fluconazole on the pharmacokinetics of IGR and M2 in rats. In the presence of 20 mg/kg fluconazole (experimental group), we found the main pharmacokinetic parameters were significantly altered when compared with 2.5 mg/kg IGR alone (control group). Among them, AUC
MeSH term(s)	Rats ; Animals ; Chromatography, Liquid/methods ; Tandem Mass Spectrometry/methods ; Liquid Chromatography-Mass Spectrometry ; Fluconazole ; Drug Interactions ; Chromatography, High Pressure Liquid/methods ; Reproducibility of Results ; Chromones ; Sulfonamides
Chemical Substances	iguratimod (4IHY34Y2NV) ; Fluconazole (8VZV102JFY) ; Chromones ; Sulfonamides
Language	English
Publishing date	2024-03-02
Publishing country	England
Document type	Journal Article
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2024.116079
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Article ; Online: Differential inhibition of sildenafil and macitentan on saxagliptin metabolism.

Dai, Ge-Xin / Tan, Wei / Shen, Yuxin / Lin, Dongdong / Xu, Ren-Ai / Lin, Qianmeng / Wei, Zhen

Toxicology and applied pharmacology

2024 Volume 486, Page(s) 116934

Abstract: The development of diabetes mellitus (DM) is generally accompanied by erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), which increases the use of combination drug therapy and the risk of drug-drug interactions. Saxagliptin for the ... ...

Abstract	The development of diabetes mellitus (DM) is generally accompanied by erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), which increases the use of combination drug therapy and the risk of drug-drug interactions. Saxagliptin for the treatment of DM, sildenafil for the treatment of ED and PAH, and macitentan for the treatment of PAH are all substrates of CYP3A4, which indicates their potential involvement in drug-drug interactions. Therefore, we investigated potential pharmacokinetic interactions between saxagliptin and sildenafil/macitentan. We investigated this speculation both in vitro and in vivo, and explored the underlying mechanism using in vitro hepatic metabolic models and molecular docking assays. The results showed that sildenafil substantially inhibited the metabolism of saxagliptin by occupying the catalytic site of CYP3A4 in a competitive manner, leading to the alterations in the pharmacokinetic properties of saxagliptin in terms of increased maximum plasma concentration (C
Language	English
Publishing date	2024-04-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	204477-8
ISSN	1096-0333 ; 0041-008X
ISSN (online)	1096-0333
ISSN	0041-008X
DOI	10.1016/j.taap.2024.116934
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Article ; Online: An Investigation of Pharmacokinetic Interaction of Vericiguat with Apigenin based on a Newly Developed Ultra-performance Liquid Chromatography-tandem Mass Spectrometry Assay.

Zhang, En / Chen, Chaojie / Wang, Yu / Weng, Qinghua / Xu, Ren-Ai / Lin, Jingjing

Current medicinal chemistry

2023

Abstract: Background: Vericiguat, as a new stimulator of soluble guanylate cyclase (sGC), was recently approved as a first-in-class treatment for reducing risks in patients with ejection fraction less than 45 percent and heart failure (HF) in the USA.: ... ...

Abstract	Background: Vericiguat, as a new stimulator of soluble guanylate cyclase (sGC), was recently approved as a first-in-class treatment for reducing risks in patients with ejection fraction less than 45 percent and heart failure (HF) in the USA. Objective: The main aim of the present experiment was to establish an acceptable, sensitive assay based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for quantitatively analyzing the plasma concentration levels of vericiguat in rats, and to further evaluate the effect of apigenin on the metabolism of vericiguat in vivo. Method: In sample processes, acetonitrile was finally chosen for quickly precipitating protein. The levels of vericiguat in plasma were analyzed by a Xevo TQ-S triple quadrupole tandem mass spectrometry (Milford, MA, USA) in a positive ion mode. Results: The scope of the calibration standard for vericiguat ranged from 0.5 to 1000 ng/mL, where a great linearity was acceptable. The lower limit of quantification (also called LLOQ) of vericiguat presented the sensitivity of this assay was evaluated as low as 0.5 ng/mL. Additionally, selectivity, accuracy and precision, extraction recovery, matrix effect, and stability were all verified. Subsequently, this approach also supported to assess the plasmatic concentrations of vericiguat from an interaction survey on herb-- drug, in which oral administration of apigenin (20 mg/kg) obviously increased the plasmatic levels of vericiguat and altered the pharmacokinetics of vericiguat in rats. Conclusion: These results would help us to further understand the pharmacokinetic properties of vericiguat when co-administration with apigenin, and to avoid unexpected clinical risks in the future.
Language	English
Publishing date	2023-10-06
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/0109298673258387230921090445
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Article: Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research.

Nie, Jingjing / Xia, Hailun / Liu, Ya-Nan / Yu, Yige / Xu, Ren-Ai

Frontiers in pharmacology

2023 Volume 14, Page(s) 1292354

Abstract: As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID-19) today, arbidol often involves drug-drug interactions (DDI) when treating critical patients. This study established a rapid and effective ... ...

Abstract	As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID-19) today, arbidol often involves drug-drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels
Language	English
Publishing date	2023-11-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1292354
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Article: A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat Plasma.

Li, Xia / Liu, Ya-Nan / Zhang, En / Xu, Ren-Ai / Yang, Tingyong / Luo, Shunbin

Journal of analytical methods in chemistry

2023 Volume 2023, Page(s) 3678599

Abstract: Oprozomib, as a second-generation orally bioavailable protease inhibitor (PI), is undergoing clinical evaluation for the treatment of haematological malignancies. In relapsed refractory multiple myeloma (RRMM) patients, oprozomib has shown good efficacy ... ...

Abstract	Oprozomib, as a second-generation orally bioavailable protease inhibitor (PI), is undergoing clinical evaluation for the treatment of haematological malignancies. In relapsed refractory multiple myeloma (RRMM) patients, oprozomib has shown good efficacy as a single agent or combination therapy. In this experiment, our purpose was to validate a sensitive and rapid method for the determination of oprozomib concentration in rat plasma by ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The samples were treated with acetonitrile as the precipitant and separated by gradient elution using a Waters Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7
Language	English
Publishing date	2023-07-11
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2654178-6
ISSN	2090-8873 ; 2090-8865
ISSN (online)	2090-8873
ISSN	2090-8865
DOI	10.1155/2023/3678599
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Article ; Online: The effect of Resveratrol on the pharmacokinetic profile of tofacitinib and the underlying mechanism.

Ye, Zhize / Hu, Jinyu / Wang, Jing / Liu, Ya-Nan / Hu, Guo-Xin / Xu, Ren-Ai

Chemico-biological interactions

2023 Volume 374, Page(s) 110398

Abstract: The purpose of this study was to (i) investigate the effect of CYP3A4 variants on tofacitinib metabolism, and (ii) investigate the interaction of tofacitinib with resveratrol and its underlying mechanisms. The concentration of M9, the main metabolite of ... ...

Abstract	The purpose of this study was to (i) investigate the effect of CYP3A4 variants on tofacitinib metabolism, and (ii) investigate the interaction of tofacitinib with resveratrol and its underlying mechanisms. The concentration of M9, the main metabolite of tofacitinib, was determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The results showed that the clearance rate of CYP3A4.18 variant was significantly decreased compared with CYP3A4.1, and the CYP3A4.28 variant was changed, but not statistically significant. In addition, the potential interaction of resveratrol with tofacitinib was determined based on rat liver microsomes (RLM), human liver microsomes (HLM), and CYP3A4 response systems. Resveratrol has an IC
MeSH term(s)	Rats ; Humans ; Animals ; Resveratrol/pharmacology ; Chromatography, Liquid ; Rats, Sprague-Dawley ; Cytochrome P-450 CYP3A/metabolism ; Tandem Mass Spectrometry/methods ; Microsomes, Liver/metabolism ; Chromatography, High Pressure Liquid/methods
Chemical Substances	Resveratrol (Q369O8926L) ; tofacitinib (87LA6FU830) ; Cytochrome P-450 CYP3A (EC 1.14.14.1)
Language	English
Publishing date	2023-02-09
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	218799-1
ISSN	1872-7786 ; 0009-2797
ISSN (online)	1872-7786
ISSN	0009-2797
DOI	10.1016/j.cbi.2023.110398
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Article ; Online: Effects of CYP2C19 inhibitors on mavacamten pharmacokinetics in rats based on UPLC-MS/MS.

Li, Qingqing / Liu, Ya-Nan / Chen, Chaojie / Xu, Ren-Ai / Xie, Saili / Zhan, Ruanjuan

Chemico-biological interactions

2023 Volume 380, Page(s) 110531

Abstract: Context: CYP2C19 is an important member of the human cytochrome P450 2C (CYP2C) family. Mavacamten is a novel treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) which was metabolized mainly by CYP2C19.: Objective: In ...

Abstract	Context: CYP2C19 is an important member of the human cytochrome P450 2C (CYP2C) family. Mavacamten is a novel treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) which was metabolized mainly by CYP2C19. Objective: In this study, we firstly reported and validated a quantitative analysis method of mavacamten in rat plasma based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), which was applied to the drug-drug interaction (DDI) study between mavacamten and CYP2C19 inhibitors (fluvoxamine, fluoxetine and fluconazole) in rats. Materials and methods: Vericiguat was used as the internal standard (IS), and the analyte and IS were measured with electrospray ion (ESI) source in positive ion mode on a XEVO TQ-S triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode. Results: In the scope of 1.0-100 ng/mL, this assay had excellent linearity. Both intra-day and inter-day accuracy of the analyte ranged from -2.4% to 9.1%, while the precision was ≤4.2%. Matrix effect, recovery, and stability were evaluated and validated to meet the requirements for the guidelines of bioanalytical assay. When compared with the control group, AUC Conclusions: The results showed that CYP2C19 inhibitors could significantly improve the bioavailability of mavacamten in rats, which indicated that we should pay more attention to the patient's condition to prevent the occurrence of side effects when used mavacamten in combination with CYP2C19 inhibitors.
MeSH term(s)	Rats ; Humans ; Animals ; Chromatography, Liquid ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid/methods ; Tandem Mass Spectrometry/methods ; Cytochrome P-450 CYP2C19 Inhibitors ; Cytochrome P-450 CYP2C19 ; Fluconazole/pharmacology ; Fluvoxamine/pharmacology ; Fluoxetine/pharmacology ; Reproducibility of Results
Chemical Substances	Cytochrome P-450 CYP2C19 Inhibitors ; MYK-461 ; Cytochrome P-450 CYP2C19 (EC 1.14.14.1) ; Fluconazole (8VZV102JFY) ; Fluvoxamine (O4L1XPO44W) ; Fluoxetine (01K63SUP8D) ; CYP2C19 protein, human (EC 1.14.14.1)
Language	English
Publishing date	2023-05-06
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	218799-1
ISSN	1872-7786 ; 0009-2797
ISSN (online)	1872-7786
ISSN	0009-2797
DOI	10.1016/j.cbi.2023.110531
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Article ; Online: Evaluation of the inhibitory effect of quercetin on the pharmacokinetics of tucatinib in rats by a novel UPLC–MS/MS assay

Zhang, Ying / Liu, Ya'nan / Xie, Saili / Xu, Xuegu / Xu, Ren-ai

Pharmaceutical Biology. 2022 Dec. 31, v. 60, no. 1 p.621-626

2022

Abstract: Tucatinib (CYP2C8 substrate) and quercetin (CYP2C8 inhibitor) are two common drugs for the treatment of cancer. However, the effect of quercetin on the metabolism of tucatinib remains unknown. We validated a sensitive method to quantify tucatinib levels ... ...

Abstract	Tucatinib (CYP2C8 substrate) and quercetin (CYP2C8 inhibitor) are two common drugs for the treatment of cancer. However, the effect of quercetin on the metabolism of tucatinib remains unknown. We validated a sensitive method to quantify tucatinib levels in rat plasma based on ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS), which was successfully employed to explore the effect of quercetin on tucatinib pharmacokinetics in rats. An Acquity UPLC BEH C18 column was applied to achieve the separation of tucatinib and internal standard (IS) talazoparib after protein precipitation with acetonitrile. Then, we used this assay to investigate the effect of different doses of quercetin (25, 50 and 100 mg/kg) on the exposure of orally administered tucatinib (30 mg/kg) in 24 Sprague-Dawley (SD) rats, which were randomly divided into three quercetin pre-treated groups and one control group (n = 6). Our developed assay was verified in all aspects of bioanalytical method validation, involving lower limit of quantification (LLOQ), selectivity, accuracy and precision, calibration curve, extraction recovery, matrix effect and stability. After pre-treatment with 100 mg/kg quercetin, AUC₀→ ₜ, AUC₀→∞ and C ₘₐₓ of tucatinib were remarkably increased by 75.4%, 75.8% and 59.1% (p < 0.05), respectively, while CLz/F was decreased significantly by 47.3% (p < 0.05) when compared with oral administration of 30 mg/kg tucatinib alone. This change is dose-dependent. This study will help better understand the pharmacokinetic properties of tucatinib with concurrent use with quercetin, and more clinical verifications were inspired to confirm whether this interaction has clinical significance in humans.
Keywords	acetonitrile ; calibration ; dose response ; liquid chromatography ; oral administration ; pharmacokinetics ; quercetin ; rats ; tandem mass spectrometry ; Drug–drug interaction ; cancer treatment ; HER2-positive breast cancer
Language	English
Dates of publication	2022-1231
Size	p. 621-626.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	1440131-9
ISSN	1744-5116 ; 1388-0209
ISSN (online)	1744-5116
ISSN	1388-0209
DOI	10.1080/13880209.2022.2048862
Database	NAL-Catalogue (AGRICOLA)

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