Rapid LC-MS/MS Method Accurately Quantifies Carfilzomib in Multiple Myeloma Patient Plasma, Supporting TDM

Multiple myeloma (MM) is a challenging hematological malignancy, with proteasome inhibitors (PIs) like carfilzomib forming a cornerstone of therapy. Despite their efficacy, patient response varies, and drug resistance is a significant clinical hurdle, especially in relapsed/refractory cases. Optimizing carfilzomib dosing is critical to maximize therapeutic benefit while minimizing toxicity. Therapeutic drug monitoring (TDM) offers a strategy to personalize treatment, but requires sensitive and robust analytical methods to accurately measure drug concentrations in patient samples. This gap in precise, efficient quantification methods hinders widespread TDM implementation for carfilzomib.

Researchers developed and validated a rapid LC-MS/MS method for quantifying carfilzomib in human plasma. Plasma samples were pre-processed using protein precipitation with acetonitrile. Chromatographic separation was performed on a C18 column (2.1 mm × 100 mm, 3.5 µm) at 40 °C, using a mobile phase of ACN and 10 mmol/L ammonium acetate in water (80:20, v/v) at a flow rate of 0.35 mL/min. The primary endpoint was method validation, assessing linearity, intra-day and inter-day precision, accuracy, and recovery rates to ensure its suitability for therapeutic drug monitoring.

The developed LC-MS/MS method demonstrated excellent analytical performance for carfilzomib quantification. > The method achieved outstanding linearity across a broad concentration range of 2.00-1000.00 ng/mL, confirming its suitability for measuring therapeutic drug levels in patients. Both intra-day and inter-day precision and accuracy were observed to be high, indicating reliable and reproducible measurements over time. Furthermore, the recovery rates for carfilzomib were robust, ranging from 84.1% to 93.0%, ensuring efficient extraction and accurate quantification from plasma samples. These validation parameters confirm the method's sensitivity and robustness, making it highly effective for precise determination of carfilzomib concentrations in plasma from multiple myeloma patients.