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

Schisandrin B (Sch B) is an active component in Schisandra chinensis exerting anti-cancer effect, but the mechanism is obscure. This study was designed to explore the mechanism of Sch B against colorectal cancer (CRC).

Schisandrin B exerts anti-colorectal cancer effect through CXCL2/ERK/DUSP11 signaling pathway.

 To establish and validate a sensitive and robust gas chromatography-mass spectrometry (GC-MS) method for the quantification of β-elemene in human plasma and assess the correlation between antitumor effect and β-elemene concentration .  The chromatographic column was HP-5 ms (30 m × 0.25 mm, 0.25 μm, Agilent, United States of America). The carrier gas was helium (purity > 99.5%). The flow rate was 1.0 mL/min and the total run time was 11.0 min. The plasma sample was pretreated with protein precipitation plus liquid-liquid extraction. Cancer patients were enrolled and their samples were collected for analysis.  Calibration range of β-elemene was 200.0-20,000.0 ng/mL, with correlation coefficients > 0.99. The intra- and interday precision and accuracy were less than 5.8% and within the range of -10.4%-6.6%. The exposure level of β-elemene in the responder group ranged from 278.13 to 11,886.27 ng/mL, with a median of 3568.91 ng/mL, while in the nonresponder group, the range was from 675.92 to 9716.52 ng/mL, with a median of 3351.94 ng/mL. No difference was found in the β-elemene exposure level between the two groups ( > 0.05).  This method was effectively developed, validated, and utilized to quantify β-elemene in cancer patients. The initial findings indicated no significant relationship between therapeutic efficacy and the concentration of β-elemene.

Quantification of β-Elemene by GC-MS and Preliminary Evaluation of Its Relationship With Antitumor Efficacy in Cancer Patients.

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
Schisandrin B exerts anti-colorectal cancer effect through CXCL2/ERK/DUSP11 signaling pathway. Cancer cell international\| PubMed ID: 40089741	2025
Quantification of β-Elemene by GC-MS and Preliminary Evaluation of Its Relationship With Antitumor Efficacy in Cancer Patients. Journal of analytical methods in chemistry\| PubMed ID: 40201224	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

Liya Ye

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