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

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
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

Zhenhui Jiang

Biography

JoVE Journal Publications

Other Publications