development-validation-rapid-lc-msms-method-for-carfilzomib

Development and Validation of a Rapid LC-MS/MS Method for Carfilzomib Quantification in Plasma from Multiple Myeloma Patients

Carfilzomib, a second-generation proteasome inhibitor, requires therapeutic drug monitoring (TDM). This study aimed to develop and validate a sensitive ...

Yunnan University of Chinese Medicine

Second Affiliated Hospital of Naval Medical University

Here, we provide a protocol for reliable isolation and subculture of putative mesenchymal stem cells from mice colons. This method provides a good approach to cultivate and characterize putative colonic mesenchymal stem cells (cMSCs). A high purity of cMSCs can be obtained according to this protocol. The whole isolation processes of cMSCs take about 2 h with two important digestion steps involved. Only with common culture medium, maturation of cMSCs in culture proceeds approximately 2 weeks to allow relevant researches to be conducted. This protocol sheds light on better cultivation of MSCs in vitro from post-natal colon tissues. These putative cMSCs share common phenotypic property with those in vivo reported, and contain potential lineage differentiation capacity. The successful culture of cMSCs in vitro provides an ideal model for study of MSCs biology in the intestine.

Isolation and characterization of putative mesenchymal stem cells from mammalian gut.

Kunxian capsules (KCs), a Chinese patent medicine, have been clinically proven to be effective in the treatment of rheumatoid arthritis (RA). However, the chemical profile of KC remains to be characterized, and the mechanism underlying the protective effect against RA is yet to be elucidated. Here, a network pharmacology-based approach was adopted, integrated with the chemical profiling of KC by UHPLC-Q-TOF/MS. As a result, a total of 67 compounds have been identified from KC extract, among which 43 were authenticated by comparison to the mass spectrum of standard chemicals. ADME behaviors of the chemical constituents of KC were predicted, resulting in 35 putative active ingredients. Through target prediction of both active ingredients of KC and RA and PPI analysis, core targets were screened out, followed by biological process and related pathway enrichment. Then, a TCM-herb-ingredient-target-pathway network was constructed and a multicomponent, multitarget, and multipathway synergistic mechanism was proposed, providing an information basis for further investigation. The active pharmaceutical ingredients included mainly terpenoids (such as triptolide and celastrol), sesquiterpene pyridines (such as wilforgine and wilforine), and flavonoids (such as icariin, epimedin A, B, and C, and 2″-O-rhamnosylicariside II).

Network Pharmacology-Based Analysis on the Curative Effect of Kunxian Capsules against Rheumatoid Arthritis.

Idiopathic pulmonary fibrosis (IPF), characterized by excessive collagen deposition, is a progressive and typically fatal lung disease without effective therapeutic methods. Tanreqing injection (TRQ), a Traditional Chinese Patent Medicine, has been widely used to treat inflammatory respiratory diseases clinically.

Tanreqing injection protects against bleomycin-induced pulmonary fibrosis via inhibiting STING-mediated endoplasmic reticulum stress signaling pathway.

Acute lung injury (ALI), a progressive lung disease mostly caused by sepsis, is characterized by uncontrolled inflammatory responses, increased oxidative stress, pulmonary barrier dysfunction, and pulmonary edema. Ursodeoxycholic acid (UDCA) is a natural bile acid with various pharmacological properties and is extensively utilized in clinical settings for the management of hepatobiliary ailments. Nonetheless, the potential protective effects and mechanism of UDCA on sepsis-induced lung injuries remain unknown. In this study, we reported that UDCA effectively inhibited pulmonary edema, inflammatory cell infiltration, pro-inflammatory cytokines production, and oxidative stress. Furthermore, UDCA treatment significantly alleviated the damage of pulmonary barrier and enhanced alveolar fluid clearance. Importantly, UDCA treatment potently suppressed PANoptosis-like cell death which is demonstrated by the block of apoptosis, pyroptosis, and necroptosis. Mechanistically, UDCA treatment prominently inhibited STING pathway. And the consequential loss of STING substantially impaired the beneficial effects of UDCA treatment on the inflammatory response, pulmonary barrier, and PANoptosis. These results indicate that STING plays a pivotal role in the UDCA treatment against sepsis-induced lung injury. Collectively, our findings show that UDCA treatment can ameliorate sepsis-induced lung injury and verified a previously unrecognized mechanism by which UDCA alleviated sepsis-induced lung injury through blocking PANoptosis-like cell death via STING pathway.

Ursodeoxycholic acid alleviates sepsis-induced lung injury by blocking PANoptosis via STING pathway.

This study aims to explore the mechanism underlying the induction of phlebitis by aescinate and create an early-warning model of phlebitis based on metabolomics.

Exploring the Occurrence Mechanism and Early-Warning Model of Phlebitis Induced by Aescinate Based on Metabolomics in Cerebral Infarction Patients.

Since the first experimentally proven tyrosine kinase inhibitor (TKI) imatinib was introduced in the clinical setting, TKIs have attracted widespread attention because of their remarkable therapeutic effects and improvement of survival rates. TKIs are small-molecule, multi-target, anti-cancer agents that target different tyrosine kinases and block downstream signaling.

Tyrosine kinase inhibitor-induced hypothyroidism: mechanism and clinical implications.

Diarrhea is the primary dose-limiting side effect of capecitabine(Cap) hindering its clinical application, but the mechanism is unclear. Clarifying this mechanism may enhance the patient compliance and improve the treatment outcome.

Disturbance of bile acids profile aggravates the diarrhea induced by capecitabine through inhibiting the Wnt/β-catenin pathway.

Corrigendum to "Disturbance of bile acids profile aggravates the diarrhea induced by capecitabine through inhibiting the Wnt/β-catenin pathway" [J. Adv. Res. 72 (2025) 591-604].

A rapid and quantitative analytical method for the detection of isepamicin (ISP) in human plasma was developed utilizing ultra-high performance liquid chromatography coupled with tandem triple quadrupole mass spectrometry (UHPLC-MS/MS). This method facilitates the monitoring of ISP plasma concentrations to examine distribution trends and the incidence of adverse reactions post-administration. Furthermore, the safety profile of ISP in clinical applications was evaluated from a therapeutic perspective by correlating ISP levels with patients' clinical recovery, thereby providing a reference framework for assessing ISP's safety.

Development and application of a method for quantitative monitoring of Isepamicin concentration in human plasma based on liquid chromatography-mass spectrometry.

The purpose of this study is to develop and validate a simple and rapid analytical method using ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous quantification of two commonly used contrast agents, iopromide and iodixanol, in human plasma. The separation of two compounds was analyzed utilizing an Agilent ZORBAX SB-C column (2.1 × 100 mm, 3.5 μm) with an isocratic elution procedure. The mobile phase consisted of acetonitrile and 0.2% formic acid aqueous solution (14:86, V:V). A simple protein precipitation method was used to pretreat plasma samples. The iopromide and iodixanol exhibited excellent linearity between 2.0 and 400.0 μg/mL, with both  values exceeding 0.99. Recovery of iopromide ranged from 91.39% to 102.69%, and matrix effect varied between 87.88% and 104.08%; the relative standard deviation (RSD%) of intra- and interday precisions fell within the range of 1.29%-4.7%. For iodixanol, recovery ranged from 97.68% to 100.14%, and the matrix effect was between 87.88% and 96.64%, and RSD% values of intra- and interday precisions ranged from 1.58% to 8.2%. Method validation results all met methodological criteria. The UHPLC-MS/MS method was successfully developed and validated and then applied to determine two common contrast agents, iopromide and iodixanol, in human plasma.

Development and Application of Analytical Method for Simultaneous Quantification of Iopromide and Iodixanol in Human Plasma.

Local drug exposure is closely associated with both therapeutic efficacy and adverse reactions. Anlotinib is approved for the treatment of chemotherapy-refractory or metastatic non-small cell lung cancer; its clinical application is limited by severe adverse reactions, particularly hypertension and diarrhea, and the relationship between intracellular exposure and toxicity remains unclear. In this study, a rapid and sensitive UHPLC-MS/MS method was developed using an Agilent 1290-6460A ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer to quantify anlotinib in human intestinal epithelial cells (HIECs) and human umbilical vein endothelial cells (HUVECs). Pazopanib-d3 was employed as an internal standard, and anlotinib was accurately quantified in 10-4000 ng/mL in positive ionization mode, with acceptable specificity, linearity, accuracy, precision, stability, and dilution integrity. The method was successfully applied to determine intracellular and extracellular anlotinib concentrations in HIECs and HUVECs. Notably, significant differences were observed between intracellular and extracellular concentrations, and intracellular anlotinib concentrations, rather than extracellular concentrations, were positively correlated with cytotoxicity in both cell types. Collectively, this study established a robust analytical approach for intracellular anlotinib quantification and provided experimental evidence linking intracellular exposure to cytotoxicity, offering a foundation for further investigation of anlotinib-induced adverse reactions.

Article	Year
Isolation and characterization of putative mesenchymal stem cells from mammalian gut. Cytotechnology\| PubMed ID: 27757711	2016
Network Pharmacology-Based Analysis on the Curative Effect of Kunxian Capsules against Rheumatoid Arthritis. Evidence-based complementary and alternative medicine : eCAM\| PubMed ID: 34630616	2021
Tanreqing injection protects against bleomycin-induced pulmonary fibrosis via inhibiting STING-mediated endoplasmic reticulum stress signaling pathway. Journal of ethnopharmacology\| PubMed ID: 36584920	2023
Ursodeoxycholic acid alleviates sepsis-induced lung injury by blocking PANoptosis via STING pathway. International immunopharmacology\| PubMed ID: 37948864	2023
Exploring the Occurrence Mechanism and Early-Warning Model of Phlebitis Induced by Aescinate Based on Metabolomics in Cerebral Infarction Patients. Journal of inflammation research\| PubMed ID: 38260811	2024
Tyrosine kinase inhibitor-induced hypothyroidism: mechanism and clinical implications. European journal of clinical pharmacology\| PubMed ID: 38483545	2024
Disturbance of bile acids profile aggravates the diarrhea induced by capecitabine through inhibiting the Wnt/β-catenin pathway. Journal of advanced research\| PubMed ID: 39048073	2025
Corrigendum to "Disturbance of bile acids profile aggravates the diarrhea induced by capecitabine through inhibiting the Wnt/β-catenin pathway" [J. Adv. Res. 72 (2025) 591-604]. Journal of advanced research\| PubMed ID: 40592668	2025
Development and application of a method for quantitative monitoring of Isepamicin concentration in human plasma based on liquid chromatography-mass spectrometry. Journal of pharmacological sciences\| PubMed ID: 41326288	2026
Development and Application of Analytical Method for Simultaneous Quantification of Iopromide and Iodixanol in Human Plasma. International journal of analytical chemistry\| PubMed ID: 41477355	2025
An LC-MS/MS-Based Quantification of Intracellular Anlotinib Reveals Exposure-Toxicity Relationships in Endothelial and Intestinal Epithelial Cells. Biomedical chromatography : BMC\| PubMed ID: 41603255	2026

Xia Tao

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