Quantification of lenalidomide and pomalidomide enantiomers in multiple myeloma patients: An exploratory study

BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disorder representing 1.8% of all cancers. Immunomodulatory drugs such as lenalidomide (LND) and pomalidomide (PMD) are crucial for treating MM. This study developed and validated a novel chiral stationary phase high-performance liquid chromatography (CSP-HPLC) method to quantify LND and PMD enantiomers in human plasma. METHODOLOGY: The study included 12 MM patients (6 on LND, 6 on PMD) in their second chemotherapy cycle. Blood samples were collected for trough and crest levels. The CSP-HPLC method successfully separated and quantified the enantiomers of both drugs. RESULTS: For LND, the S-(-) enantiomer showed mean trough and crest concentrations of 11.98 ng/mL and 211.44 ng/mL, respectively. The R-(+) enantiomer had mean trough and crest concentrations of 11.13 ng/mL and 199.86 ng/mL. For PMD, enantiomer-I showed mean trough and crest concentrations of 1.68 ng/mL and 71.45 ng/mL, while enantiomer-II had 1.06 ng/mL and 69.54 ng/mL, respectively. CONCLUSION: The study demonstrated that the S-enantiomer of LND and enantiomer-I of PMD had slightly higher plasma concentrations and potentially greater antimyeloma activity. These findings provide a basis for developing enantiomeric compounds of LND and PMD, which could lead to more effective and safer treatments for MM.