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

A novel chiral stationary phase HPLC (CSP-HPLC) method was developed and validated that successfully separated and quantified the enantiomers of lenalidomide and pomalidomide in human plasma.

• The method resolved both LND enantiomers (S-(-) and R-(+)) and both PMD enantiomers (designated enantiomer-I and enantiomer-II).
• The method was applied to plasma samples from multiple myeloma patients.
• The abstract describes the method as both developed and validated.

In patients receiving lenalidomide, the S-(-) enantiomer had slightly higher mean trough and crest plasma concentrations than the R-(+) enantiomer.

• S-(-) LND: mean trough 11.98 ng/mL and mean crest 211.44 ng/mL.
• R-(+) LND: mean trough 11.13 ng/mL and mean crest 199.86 ng/mL.
• Six patients were on LND, all in their second chemotherapy cycle.

In patients receiving pomalidomide, enantiomer-I had slightly higher mean trough and crest plasma concentrations than enantiomer-II.

• PMD enantiomer-I: mean trough 1.68 ng/mL and mean crest 71.45 ng/mL.
• PMD enantiomer-II: mean trough 1.06 ng/mL and mean crest 69.54 ng/mL.
• Six patients were on PMD, all in their second chemotherapy cycle.

Crest concentrations were far higher than trough concentrations for both drugs' enantiomers, and lenalidomide concentrations were higher than pomalidomide concentrations.

• LND crest values were about 200-211 ng/mL versus troughs of about 11-12 ng/mL.
• PMD crest values were about 70-71 ng/mL versus troughs of about 1-1.7 ng/mL.
• This comparison is derived from the reported mean values.

The authors concluded that the S-enantiomer of LND and enantiomer-I of PMD, having slightly higher plasma concentrations, may have greater antimyeloma activity, providing a basis for developing enantiomeric formulations.

• The study was exploratory with 12 MM patients (6 LND, 6 PMD).
• The authors state the findings could lead to more effective and safer treatments for MM.
• The activity inference is described as 'potentially' greater, based on concentration differences.

Multiple myeloma is a malignant plasma cell disorder representing 1.8% of all cancers, and immunomodulatory drugs such as LND and PMD are crucial for its treatment.

• LND and PMD are chiral compounds, motivating enantiomer-specific quantification.
• Blood samples were collected at trough and crest time points.