Lenalidomide, a blockbuster drug for the treatment of multiple myeloma: Semipreparative separation through supercritical fluid chromatography and vibrational circular dichroism spectroscopy

Abstract

Semipreparative separation of lenalidomide has been performed through supercritical fluid chromatography. In regard to retention and resolution of lenalidomide, effects of chromatographic conditions, such as chiral stationary phases, organic co-solvents, mobile phases, and column temperature, have been studied in detail. Amylose tris(3, 5-dimethylphenylcarbamate)-coated and the single-urea-bound β-cyclodextrin chiral stationary phases exhibited good separation performances for lenalidomide in the CO /methanol mixture. Then, a comparative study of semipreparative separation of lenalidomide has been carried out on these two chiral stationary phases. As indicated, separation of lenalidomide on the β-cyclodextrin-bound column was much better than the other. Under the optimized conditions, the loading per injection was 30 mg, the cycle time was 5 min, and the recoveries of two enantiomers were about 81.7 and 79.5%, respectively. Moreover, the vibrational circular dichroism spectrum of the first-eluted enantiomer in d -dimethylsulfoxide solution was consistent with the calculated pattern based on the S configuration, revealing that it should be (S)-(-)-lenalidomide. Briefly, this separation method through supercritical fluid chromatography might provide favorable information for rapid separation, enantioselective assessment, and absolute configurations of chiral pharmaceuticals.

HPLC semi‐preparative separation of diclazuril enantiomers and racemization in solution

“…CSPs, organic modifiers, and column temperature have greatly affected chiral separation of analytes . Systematic exploration for chromatographic factors will help us develop suitable conditions for analysis, determination, and preparative separation of chiral pharmaceuticals.…”

Identification, Quantification, and Stereoselective Degradation of Triazole Fungicide Cyproconazole in Two Matrixes through Chiral Liquid Chromatography-Tandem Mass Spectrometry

“…With the development of the theoretical framework, especially the application of DFT to the calculation of VCD spectra, VCD spectroscopy has become a powerful tool in confirmation of absolute configurations and characterization of chiroptical properties of chiral compounds and natural products in recent years. ,,− Herein, four cyproconazole stereoisomers were obtained through supercritical fluid chromatography semipreparative separation (presented in Figure S1 of the Supporting Information) and denoted as P1, P2, P3, and P4 according to elution order from the EnantioPak OD chiral column under the optimized chromatographic conditions, respectively. Enantiomeric excess purities of them were 99.2%, 97.3%, 99.3%, and 99.6%, respectively (Figure S2).…”

“…Measurement of the IR-VCD spectra of four cyproconazole stereoisomers was performed in a BioTools ChiralIR-2X dual photoelastic modulator VCD spectrometer, according to similar procedures outlined in our previous publications. , The resolution and ZnSe photoelastic modulator was 4 and 1400 cm –1 (for the fingerprint region), respectively. Cyproconazole in CDCl 3 solution was injected into the sample cell (150 mm in optical length) with BaF 2 windows.…”

Chiral analysis and semi‐preparative separation of metconazole stereoisomers by supercritical fluid chromatography and cytotoxicity assessment in vitro

“…Note that, 10 μL Metconazole solutions in methanol (1 mg⋅mL −1 ) were injected into the chromatographic system in triplicate. The separation parameters of metconazole, namely resolution (R s ), retention factor (k), and selectivity factor (α), were calculated using standard formulas reported in the literature [14,15].…”

“…Semi‐preparative separation of dihydromyricetin was performed on an amylose tris(3,5‐dimethylphenylcarbamate)‐coated CSP with the CO 2 ‐methanol mixture, in which the productivity was 0.27 g (racemate)/g (CSP)/24 h when sample loading per injection was 120 mg, and the consumption of methanol was estimated to be 1.76 L/g (racemate) [14]. Semi‐preparative separation of lenalidomide enantiomers through SFC resulted in ten‐fold higher productivity and seven‐fold lower solvent consumption than the reported HPLC method [15].…”