Comparative Chiral Separation of Thalidomide Class of Drugs Using Polysaccharide-Type Stationary Phases with Emphasis on Elution Order and Hysteresis in Polar Organic Mode

The enantioseparation of four phthalimide derivatives (thalidomide, pomalidomide, lenalidomide and apremilast) was investigated on five different polysaccharide-type stationary phases (Chiralpak AD, Chiralpak AS, Lux Amylose-2, Chiralcel OD and Chiralcel OJ-H) using neat methanol (MeOH), ethanol (EtOH), 1-propanol (PROP), 2-propanol (IPA) and acetonitrile (ACN) as polar organic mobile phases and also in combination. Along with the separation capacity of the applied systems, our study also focuses on the elution sequences, the effect of mobile phase mixtures and the hysteresis of retention and selectivity. Although on several cases extremely high resolutions (Rs > 10) were observed for certain compounds, among the tested conditions only Chiralcel OJ-H column with MeOH was successful for baseline-separation of all investigated drugs. Chiral selector- and mobile-phase-dependent reversals of elution order were observed. Reversal of elution order and hysteresis of retention and enantioselectivity were further investigated using different eluent mixtures on Chiralpak AD, Chiralcel OD and Lux Amylose-2 column. In an IPA/MeOH mixture, enantiomer elution-order reversal was observed depending on the eluent composition. Furthermore, in eluent mixtures, enantioselectivity depends on the direction from which the composition of the eluent is approached, regardless of the eluent pair used on amylose-based columns. Using a mixture of polar alcohols not only the selectivities but the enantiomer elution order can also be fine-tuned on Chiralpak AD column, which opens up the possibility of a new type of chiral screening strategy.

A NEW NP-UPLC METHOD FOR THE SEPARATION AND SIMULTANEOUS QUANTIFICATION OF RAMUCIRUMAB AND ERLOTINIB

Objective: This investigation demonstrates a stability-indicating and reliable “normal phase ultra-performance liquid chromatography” method to simultaneously quantify Ramucirumab and Erlotinib in the pharmaceutical dosage form. Methods: Successful separation was accomplished using Chiralcel-OD-3 column (50 mm x 4.6 mm, 3 μm) with an isocratic type of elution using a mobile phase containing n-hexane+isopropyl alcohol+methanol (89:10:1), respectively with 1.0 ml/min flow rate. The wavelength sensor was attuned at 266 nm to quantify Ramucirumab and Erlotinib. Results: Erlotinib and Ramucirumab peaks were eluted with fine resolution at retention times 1.7807 min and 3.175 min, respectively. In the 10-150 μg/ml and 1-15 μg/ml concentration ranges for Erlotinib and Ramucirumab, the calibration graphs were linear, with regression coefficients of 0.99928 and 0.99976, respectively. The suggested ultra-performance liquid chromatography approach has been shown as sensitive, precise, robust, accurate, specific and stability indicating through the resolution of Erlotinib and Ramucirumab from its degradation-based compounds. Conclusion: The established ultra-performance liquid chromatography technique was effectively extended to the evaluation of Erlotinib and Ramucirumab in the pharmaceutical dosage form and the test results appeared satisfactory.

Analysis of Orphenadrine Citrate in Various Chiral Stationary Phases: A Comparative Study

Background: Polysaccharide based chiral stationary phases (CSPs) were used to perform enantiomeric separation of Orphenadrine Citrate by Ultra-Fast Liquid Chromatography (UFLC) technique. Trials were conducted using the polar mode, reverse phase mode and normal phase mode. Amylose and Cellulose-based CSPs were used for the same. Materials and Methods: Eight Amylose-based CSPs and four Cellulose-based CSPs were used in the reverse phase mode. Five Amylose-based CSPs and two Cellulose-based CSPs were used in polar mode. The only Cellulose-based CSP used in the normal phase mode could effectively separate Orphenadrine Citrate enantiomers with a good resolution. Results and Discussion: Successful enantioseparation was obtained using Chiralcel OD-H containing Cellulose tris (3, 5- dimethylphenylcarbamate) as a chiral selector and n-hexane: Ethanol: Diethylamine (95: 05: 0.1, v/v/v) as the mobile phase. The developed method was validated in accordance with ICH guidelines (Q2R1). Conclusion: The proposed objectives were successfully accomplished as the developed method could effectively resolve Orphenadrine Citrate enantiomers.

Enantiomeric separation and molecular docking study of seven imidazole antifungal drugs on a cellulose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase

Chiral separation and molecular docking study of seven imidazole antifungal drugs were performed on a cellulose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase (Chiralcel OD-RH).

Determination of Four Nadolol Stereoisomers in Capsules by High-Performance Liquid Chromatography and Circular Dichroism

Nadolol is a blocking agent with activity in β-adrenergic receptors. The objective of this research was to develop and validate an HPLC and circular dichroism method for the quantification of four nadolol stereoisomers in capsules. The HPLC method was validated using a Chiralcel OD column (250 × 4,6 mm, 10 μm). The mobile phase consisted of hexane–ethanol–diethylamine–acetic acid (86 + 14 + 0.3 + 0.3, v/v/v/v), with a flow rate of 0.7 mL/min and temperature of 25 ± 1°C and UV detection carried out at 220 nm. Solutions were prepared in ethanol containing 200 μg/mL nadolol. The method proved to be precise, selective, accurate, and robust and was successfully applied for the determination of the two homologs of four nadolol stereoisomers in capsules.

Determination of Competitive Adsorption Isotherm of the Etodolac Enantiomers Using Inverse Method

The competitive adsorption isotherm of etodolac enantiomers on a cellulose carbamates-based chiral stationary phase (Chiralcel OD) at 25°C was determined in this study by the inverse method (IM). An equilibrium dispersive (ED) model combined with bi-Langmuir adsorption model was used in predicting the elution profiles. The adsorption isotherm model with 5 parameters was determined by fitting the two overloaded band profiles. The non-dominated sorting genetic algorithm (NSGA-II) and Levenberg-Marquardt algorithm (LMA) were crucial tools and utilities in this process. Suitable model parameters have been obtained and the experimental results were in good agreement with the model predictions.

Chiral Separation of Cypermethrin Enantiomers by High Performance Liquid Chromatography

The separation of cypermethrin was studied on Chiralcel OD-H column using the high performance liquid chromatography (HPLC) method. And well distinguished peaks of cypermethrin isomers were obtained. The influences of mobile phase ratios, flow rates, and detection wavelengths on the separation results were investigated. The optimal chromatographic conditions were as follows: the mobile phase ratio was hexane: isopropanol = 97:3, the flow rate was 0.4ml/min, and the wavelength was set as 236 nm. Under the optimal conditions, the resolutions of cypermethrin enantiomers were more than 2.0.