Development of UPLC-MS/MS Method for Studying the Pharmacokinetic Interaction Between Dasatinib and Posaconazole in Rats

Yang, Suili; Zhang, Xiaoshan; Wang, Yuzhen; Wen, Congcong; Wang, Chenxiang; Zhou, Ziye; Lin, Gen‐Min

doi:10.2147/dddt.s301241

Cited by 10 publications

(6 citation statements)

References 21 publications

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“…The plasma DAS concentration upon administration of unprocessed drug (dose of 10 mg kg −1 ) increased quickly, the C max was 72.5 ng mL −1 and the time to the C max (t max ) 4.0 h. Then, the drug was cleared fast with a t 1/2 of 5.1 h ( Figure 11 , Table 2 ). These results were in good agreement with the literature [80,84].…”

Section: Resultssupporting

confidence: 93%

An experimental and theoretical approach to understand the interaction between particles and mucosal tissues

Sverdlov

Cohen

Sosnik

2022

Preprint

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Nanonization of poorly water-soluble drugs has shown great potential in improving their oral bioavailability by enhancing the dissolution rate and saturation solubility. Moreover, due to particle size reduction and larger surface area, the number of contact points with the gastrointestinal mucus favors adhesion. Similar phenomena could be anticipated when nano-pollutants come into direct contact with mucosal tissues. However, the fundamental features that govern the interaction of particles with mucus have not been investigated in a systematic and rational way before. In this work, we synthesize mucin hydrogels of different pore sizes with rheological properties that closely mimic the properties of freshly extracted porcine mucin. By using fluorescent pure curcumin particles, we characterize the effect of particle size (hydrodynamic diameter of 200 nm, and 1.2 and 1.3 μm), concentration (18, 35, and 71 μg mL−1), and hydrogel crosslinking density (which is directly related to the stiffness and governs the average pore size) on the diffusion-driven particle penetration in vitro. Next, we derive a phenomenological model that describes the physics behind the diffusion-derived penetration of particles into the mucin network and considers the contributions of the particle size, the particle concentration, and the crosslinking density of the mucin hydrogel. Finally, we challenge our experimental-theoretical approach by preliminarily assessing the oral pharmacokinetics of an anti-cancer model drug, namely dasatinib, in pristine and nanonized forms and two clinically relevant doses in rats. For of a dose of 10 mg kg−1, drug nanonization leads to a significant ~8- and ~21-fold increase of the drug oral bioavailability and half-life, respectively, with respect to the unprocessed micron-sized drug. When the drug dose of pure drug nanoparticles (which is directly related to the local concentration of the drug in the gastrointestinal tract) was increased to 15 mg mL−1, the oral bioavailability increased though not significantly, suggesting the saturation of the penetration sites in the mucus, as demonstrated by the in vitro model. Our overall results reveal the potential of this experimental-theoretical approach, shed light on the interaction of particulate matter and mucosal tissues, and pave the way for the development of tools that enable a more rational design of nano-drug delivery systems for mucosal administration and the assessment of risk factors related to the exposure of mucosal tissues to nano-pollutants.

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Section: Resultssupporting

confidence: 93%

An experimental and theoretical approach to understand the interaction between particles and mucosal tissues

Sverdlov

Cohen

Sosnik

2022

Preprint

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“…The plasma concentration of lapatinib was evaluated using LC–MS/MS method. LC–MS/MS is the most commonly used method in pharmacokinetic studies due to its excellent sensitivity and efficiency ( Wang et al, 2021 ; Yang et al, 2021 ), while several methodologies using LC–MS/MS to quantify lapatinib in human or rat plasma have been published ( Alrobaian et al, 2022 ; Karbownik et al, 2020 ; Karbownik et al, 2018 ; Li, Zhao & Zhao, 2022 ), there’s no literature describing the quantification of lapatinib in rabbits. Here a sensitive and robust LC–MS/MS method was developed to quantify lapatinib in rabbit plasma.…”

Section: Discussionmentioning

confidence: 99%

Dose-sparing effect of lapatinib co-administered with a high-fat enteral nutrition emulsion: preclinical pharmacokinetic study

Zhu,

Xu,

Yang

et al. 2023

PeerJ

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Background Lapatinib is an oral small-molecule tyrosine kinase inhibitor indicated for advanced or metastatic HER2-positive breast cancer. In order to reduce the treatment cost, a high-fat enteral nutrition emulsion TPF-T was selected as a dose-sparing agent for lapatinib-based therapies. This study aimed to investigate the effect of TPF-T on lapatinib pharmacokinetics. Methods First, a simple and rapid liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed to quantitatively evaluate lapatinib in rabbit plasma. The method was fully validated according to the China Pharmacopoeia 2020 guidance. Rabbits and rats were chosen as the animal models due to their low and high bile flows, respectively. The proposed LC–MS/MS method was applied to pharmacokinetic studies of lapatinib, with or without TPF-T, in rabbit and rat plasma. Results The LC–MS/MS method revealed high sensitivity and excellent efficiency. In the rabbit model, co-administration with TPF-T resulted in a 32.2% increase in lapatinib exposure. In the rat model, TPF-T had minimal influence on the lapatinib exposure. In both models, TPF-T was observed to significantly elevate lapatinib concentration in the absorption phase. Conclusion Co-administration with TPF-T had a moderate effect on increasing exposure to lapatinib. Dose sparing using a high-fat liquid diet is potentially feasible for lapatinib-based therapies.

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“…UPLC-MS/MS has the advantages of high sensitivity, strong specificity, short analysis time, and good reproducibility. Therefore, it is often used in the detection of biological samples and the study of pharmacokinetics and DDI ( Wang et al, 2020b ; Yang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Posaconazole and Isavuconazole on the Pharmacokinetics of Erdafitinib in Beagle Dogs by UPLC-MS/MS

Ruan

Wang

et al. 2021

Front. Pharmacol.

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Objective: A robust, quick, and reliable ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method for the quantification of erdafitinib in beagle dog plasma was developed and validated to evaluate the changes of posaconazole and isavuconazole on the pharmacokinetics of erdafitinib in beagle dogs, respectively.Methods: This experiment adopted a three-period self-control experimental design. In the first period (group A), erdafitinib was orally administered to six beagle dogs at a dose of 4 mg/kg. In the second period (group B), the same six beagle dogs were orally given posaconazole at a dose of 7 mg/kg, and after 30 min, erdafitinib was orally given. In the third period (group C), isavuconazole at a dose of 7 mg/kg was given orally, and then, erdafitinib was orally given. At the different time points after erdafitinib was given in the three periods, the blood samples were collected. The concentration of erdafitinib was detected by the developed UPLC-MS/MS method. DAS 2.0 was used to calculate the pharmacokinetic parameters of erdafitinib.Results: Erdafitinib had a good linear relationship in the range of 1–500 ng/ml, and the lower limit of quantification was 1 ng/ml. The precision, accuracy, extraction recovery, matrix effect, and stability meet the requirements of the guiding principles. After erdafitinib was combined with posaconazole, the Cmax and AUC0→t of erdafitinib increased by 27.19% and 47.62%, respectively, and the t1/2 was prolonged to 6.33 h. After erdafitinib was combined with isavuconazole, the Cmax and AUC0→t of erdafitinib increased by 23.13% and 54.46%, respectively, and the t1/2 was prolonged to 6.31 h.Conclusion: A robust and reliable UPLC-MS/MS method was fully optimized and developed to detect the plasma concentration of erdafitinib in beagle dogs. Posaconazole and isaconazole could inhibit the metabolism of erdafitinib in beagle dogs and increase the plasma exposure of erdafitinib.

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Development of UPLC-MS/MS Method for Studying the Pharmacokinetic Interaction Between Dasatinib and Posaconazole in Rats

Cited by 10 publications

References 21 publications

An experimental and theoretical approach to understand the interaction between particles and mucosal tissues

An experimental and theoretical approach to understand the interaction between particles and mucosal tissues

Dose-sparing effect of lapatinib co-administered with a high-fat enteral nutrition emulsion: preclinical pharmacokinetic study

The Effect of Posaconazole and Isavuconazole on the Pharmacokinetics of Erdafitinib in Beagle Dogs by UPLC-MS/MS

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