Journal of Mass Spectrometry and Advances in the Clinical Lab
·
2023
·
IF 2.2
Fangjun Chen,Wenda Chen,Zhenxin Wang,Yingfei Peng,Beili Wang,Baishen Pan,Wei Guo
Introduction Tyrosine kinase inhibitors (TKIs) are widely used in tumor treatment. The detection of these medicines by liquid chromatography-tandem mass spectrometry (LC-MS/MS) can avoid the interference of structurally similar compounds. Objectives This study aimed to develop and validate a new LC-MS/MS assay for the quantification of eight tyrosine kinase inhibitors in human plasma and to preliminarily evaluate the clinical utility of the therapeutic drug monitoring method. Methods Plasma samples were prepared by simple protein precipitation and separated using an ultra-high-performance reversed phase column. Detection was achieved using a triple quadrupole mass spectrometer in the positive ionization mode. The assay was validated against standard guidelines. We reviewed and analyzed the results of 268 plasma samples obtained from patients administered imatinib and other TKIs collected from January 2020 to November 2021 at Zhongshan Hospital. The analytes were separated and quantified within 3.5 min. Results The newly developed method demonstrated linearity for the detected drug concentration in the range of 20 to 2000 ng/ml for gefitinib (r 2 = 0.991) and crizotinib (r 2 = 0.992), 50 to 5000 ng/ml for nilotinib (r 2 = 0.991) and imatinib (r 2 = 0.995), 1500–150,000 ng/ml for vemurafenib (r 2 = 0.998), 1000–100,000 ng/ml for pazopanib (r 2 = 0.993), 0.5–100 ng/ml for axitinib (r 2 = 0.992) and 5–500 ng/ml for sunitinib (r 2 = 0.991) and N-desethyl sunitinib (r 2 = 0.998). The lower limit of quantification (LLOQ) was 20 ng/ml for gefitinib and crizotinib, 50 ng/ml for nilotinib and imatinib, 1500 ng/ml for vemurafenib, 1000 ng/ml for pazopanib, 0.5, and 5 ng/ml for sunitinib and N-desethyl sunitinib, respectively. Specificity, precision, accuracy, and stability were tested, and met the requirements of the guidelines. At the same dose, there was no significant difference in plasma drug concentration between the original imatinib medicine and the generic medicine after patent expiration. Conclusion We developed a sensitive and reliable method for the quantification of eight TKIs.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Yunsheng Ran,Chujiao Hu,Junzhao Wan,Qian Kang,Ruixian Zhou,Ping Liu,Dan Ma,Jianta Wang,Lei Tang
Peroxisome proliferator-activated receptor gamma (PPARG), a key transcription factor involved in lipid metabolism and glucose homeostasis, has been implicated in various types of cancer. However, its precise role in cancer remains unclear. In this study, we conducted a comprehensive pan-cancer analysis of PPARG expression using various types of cancer obtained from public databases. We observed significant heterogeneity in PPARG expression across different types of cancer. The association between PPARG expression and patient prognosis was investigated using Cox proportional hazards regression models and survival analysis. Clinical features and protein expression levels in the cohort showed that PPARG expression was strongly associated, suggesting its potential as a therapeutic target. We also evaluated the prognostic potential of PPARG by analyzing immune infiltration and genomic stability. We experimentally validated the potential of PPARG as a therapeutic target by analyzing drug sensitivity profiles, molecular docking simulations, and in vitro cell proliferation assays associated with PPARG expression. We identified common expression patterns of PPARG with other genes involved in key carcinogenic pathways. This provides deeper insights into the molecular mechanisms underlying its carcinogenic role. Additionally, functional enrichment analysis revealed significant enrichment of genes related to drug metabolism, cell proliferation, and immune response pathways associated with PPARG. Our findings highlight the importance of PPARG in the broader biology of cancer and suggest its potential as a diagnostic and therapeutic target for specific types of cancer. The results of our study provide strong support for the potential role of PPARG as a promising prognostic biomarker and immunotherapeutic target across various types of cancer.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2020
·
IF 5.339
Yue-Yue Chang,Hai-Long Wu,Huan Fang,Tong Wang,Yang-Zi Ouyang,Xiao-Dong Sun,Gao-Yan Tong,Yu-Jie Ding,Ru-Qin Yu
Three intelligent chemometric multi-way calibration methods including alternating trilinear decomposition (ATLD), alternating trilinear decomposition assisted multivariate curve resolution (ATLD-MCR) and multivariate curve resolution-alternating least squares (MCR-ALS) combined with high performance liquid chromatography-diode array detection (HPLC-DAD) were used to quantify ten molecular targeted anti-tumor drugs in three complex biological matrices (plasma, urine and cell culture media matrices). All analytes can be successfully eluted in 6.5 min. In this experiment, various degrees of time shifts occurred in different samples. While slight time shifts exist in the chromatographic analysis , satisfactory results can be obtained by the three proposed methods. When the time shift was large (5.6 s), the average spiked recoveries obtained by ATLD analysis were in the range of 58.9%–116.5%, which was less than satisfactory. However, the average recoveries obtained by MCR-ALS and ATLD-MCR analysis were 89.8%–114.8% and 84.5%–106.1% respectively, and more satisfactory results were obtained. For further research, ATLD-MCR and MCR-ALS methods were compared, and the results were evaluated by statistical tests. Accuracies of concentrations obtained by them were considered to be no significant difference. In addition, compared with other methods currently published, the proposed chemometric methods combined with the HPLC-DAD can rapidly, simultaneously and accurately determine varieties of molecular targeted anti-tumor drugs in different complex biological matrices even in the presence of severe peak overlaps, severe time shifts, slight baseline drifts and different unknown background interferences.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2021
·Vol. 44
·期 21
·3914-3923
·
IF 3.645
Zhao-Yang Wang,Hai-Long Wu,Yue-Yue Chang,Tong Wang,Wei Chen,Gao-Yan Tong,Ru-Qin Yu
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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Weizhen Chen,Kui Xu,Bailong Tao,Liangliang Dai,Yonglin Yu,Caiyun Mu,Xinkun Shen,Yan Hu,Ye He,Kaiyong Cai
We used surface-modified titanium (Ti) substrates with a multilayered structure composed of chitosan-catechol (Chi-C), gelatin (Gel) and hydroxyapatite (HA) nanofibers , which were previously shown to improve osteogenesis, as a platform to investigate the interaction of osteogenesis and angiogenesis during bone healing . Combined techniques of Transwell co-culture, wound healing assay , enzyme linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemical staining were used to evaluate adhesion, morphology and migration of adipose-derived mesenchymal stem cells (Ad-MSCs) and human umbilical vein endothelial cells (HUVECs) grown on different Ti substrates. We investigated the effect of substrates on the osteogenic differentiation of Ad-MSCs and reciprocal paracrine effects of Ad-MSCs on HUVECs or vice versa . The multilayered Ti substrates directly regulated the cellular functions of Ad-MSCs and angiogenic HUVECs and mediated communication between them by enhancing paracrine effects via cell–matrix interactions in vitro . The in vivo results showed that the change of microenvironment induced by surface-modified Ti implants promoted the adhesion, recruitment and proliferation of MSCs and facilitated coupled osteogenesis and angiogenesis in bone healing. The study proved that multilayer-film-coated Ti substrates positively mediated cellular biological function in vitro and improved bone healing in vivo . Statement of Significance Recent studies have revealed that osteogenesis and angiogenesis are coupled, and that communication between osteoblasts and endothelial cells is essential for bone healing and remodeling processes; however, these conclusions only result from in vitro studies or in vivo studies using transgenic murine models. Relatively little is known about the communication between osteoblasts and endothelial cells in peri-implants during bone healing processes. Our results revealed the cellular/molecular mechanism of how multilayered Ti substrates mediate reciprocal paracrine effects between adipose-derived mesenchymal stem cells and human umbilical vein endothelial cells; moreover, the interactions between the cell-matrix and peri-implant was proven in vivo with enhanced bone healing. This study contributes to our understanding of the fundamental mechanisms of angiogenesis and osteogenesis that affect peri-implantation, and thus, provides new insights into the design of future high-quality orthopedic implants.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Jianshuo Su,Jie Xu,Shufan Liu,Laura Machin Galarza,Shuangfeng Li,Huaizhen Zhang,Zhuang Ding,Jun Han,Min Liu,Yanna Zhao
The efficacy of axitinib (Axi) for treating various cancers has been demonstrated clinically. However, the poor aqueous solubility of Axi limits its application. In this study, the solubility enhancement and recrystallization inhibition effect of different cellulose derivatives and surfactants were evaluated systematically. Ternary amorphous solid dispersions of Axi (Axi TSDs) were prepared with hypromellose succinate HF (HPMCAS HF) as a recrystallization inhibitor and polyoxyethylene hydrogenated castor oil as the wetting agent. Binary amorphous solid dispersions of Axi (Axi BSDs) were also prepared with mere HPMCAS HF for further comparative study. Distinct liquid−liquid phase separation state of Axi was revealed in the binary and ternary system. Differential scanning calorimetry and powder X-ray diffraction assays confirmed that the crystalline state of Axi had successfully transformed to an amorphous state in both Axi BSDs and Axi TSDs, with morphological validation provided by scanning electron microscopy. Energy dispersive spectrometer and Fourier transform infrared spectroscopy demonstrated homogeneous excipient distribution around Axi, mediated through physical molecular interaction. Axi TSDs exhibited superior dissolution profiles in different pH media and simulated gastrointestinal fluid compared to Axi BSDs and Axi bulk powder. Pharmacokinetic evaluation in rats of Axi TSDs revealed significantly enhanced bioavailability, with an area under the plasma concentration-time curve value 2.1 times higher than Axi bulk powder and 1.5 times higher than Axi BSDs. These findings established the ternary amorphous system as a robust platform for enhancing the biopharmaceutical performance of hydrophobic therapeutics.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Meng Zhang,Yumei Wang,Jiayi Wang,Jiayi Zuo,Feng Jiang,Feng Cao
Neovascular ocular diseases are a leading cause of irreversible vision loss. Although intravitreal anti-VEGF therapy is the standard treatment, its invasive delivery and limited efficacy in some patients emphasize the need for non-invasive strategies targeting multiple angiogenic pathways. In this study, we developed a novel hybrid nanoplatform for the non-invasive co-delivery of axitinib (Axi) and telmisartan (Tel) to synergistically inhibit both VEGF and Ang-2 signaling pathways. Poorly soluble drugs were incorporated into layered double hydroxides (LDHs) via a micelle-assisted intercalation strategy and subsequently modified with hyaluronic acid (HA) conjugated to Gly-Val-Sar (GVS), a novel PepT1-targeted tripeptide. The Zn-containing LDH provided controlled drug release, and exhibited anti-inflammatory properties. HA modification prolonged ocular retention, and GVS enhanced transmembrane transport. The resulting Axi/Tel-D@LDH-HA-GVS nanocomposites demonstrated favorable physicochemical properties, efficient uptake by human conjunctival and retinal pigment epithelial cells, and potent inhibition of hypoxia-induced angiogenesis in vitro. In vivo, the formulations exhibited prolonged ocular retention, effective posterior tissue distribution, and good biosafety. In a diabetic retinopathy model, Axi/Tel-D@LDH-HA-GVS nanocomposites restored retinal structure and markedly reduced the expression of VEGF, Ang-2, TNF-α, and IL-6. Collectively, this study provides a promising non-invasive and synergistic strategy for targeted treatment of ocular neovascular diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jianshuo Su,Shufan Liu,Zhuang Ding,Cuiying Zhang,Sisi Liu,Huaizhen Zhang,Jun Han,Zhengping Wang,Min Liu,Yanna Zhao
Ophthalmic drug delivery faces significant challenges, including the poor solubility of hydrophobic agents, as well as limited permeability and rapid clearance caused by the eye’s intricate anatomical and physiological barriers. In this study, laser-triggered core–shell structural liposomal nanoparticles (Lips-NPs@Axi/Vp) were designed for precise drug delivery and offered a potential treatment strategy for ocular neovascularization by incorporating both antiangiogenic and photodynamic therapy. Laser-triggered in vitro release and intensive reactive oxygen species (ROS) production of Lips-NPs@Axi/Vp were noted. Furthermore, Lips-NPs@Axi/Vp markedly suppressed cell proliferation and tube formation of EA.hy.926 cells while revealing minimal toxicity toward human corneal epithelial cells (HCECs). Besides, the liposomal nanoparticle system exhibited extended corneal residence time exceeding 4 h, significantly facilitating drug bioavailability. Through their combined anti-inflammatory, photodynamic, and anti-VEGF effects, Lips-NPs@Axi/Vp successfully maintained corneal clarity and prevented alkali-burn-induced corneal neovascularization in animal models. The findings suggested that this multifunctional nanotherapeutic system represented a potential breakthrough for treating neovascular ocular diseases and offered significant advantages over traditional eye medications through its extended duration of action and improved therapeutic response.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）