Quantitative Chiral Separations of the Norepinephrine Reuptake Blocker Viloxazine by PO-HPLC–DAD: Application to Evaluate the Influence of Elevated Temperature and Varied pH on Chiral Interconversion
摘要
Chiral interconversion studies are crucial to unveil the inherent enantiomeric stability of a chiral pharmaceutical. Viloxazine is the chiral molecule, acting as a norepinephrine reuptake inhibitor used for the treatment of attention-deficit hyperactivity disorder (ADHD). Though viloxazine has a chiral centre, a comprehensive investigation of the enantiomeric stability under abiotic conditions remains unexplored. To bridge this gap, current research focused on the development of a rapid, accurate, and reliable analytical HPLC–DAD technique to study chiral interconversion. The chiral separation was carried out with a polar organic mode, in which 0.2% diethylamine in methanol is considered as the mobile phase and CHIRALCEL OD-H column (250 × 4.6 mm, 5 µm) as the stationary phase. The developed chiral technology was found linear in 0.10–3.00 µg mL−1 concentrations, with the correlation coefficient R2 > 0.999. The method was sensitive, able to detect at 0.03 µg mL−1, and quantify at 0.10 µg mL−1 concentrations. The technique was fully validated, and the results closely aligned with the ICHQ2 (R2) acceptance criteria. Further, the validated method was successfully applied to uncover the pH-controlled chiral interconversion behaviour. The experiments revealed that (R)-VIL was interconverted to (S)-VIL at 80 ℃ in pH 7.4 and 9.5 buffers with the change in chiral purity of 1.47% and 2.02%, respectively. The current research provides insights to the academic and industrial communities in defining the storage parameters, choosing an appropriate formulation, and identifying interactions between the medicine and the excipient, solvent, and other chemicals. Further, this novel, accurate, precise, and robust enantioselective method will be helpful in regular quality control laboratories for obtaining the chiral purity and other related information.