Rapid Screening of Volatile Ion-Pair Reagents Using UHPLC and Robust Analytical Method Development Using DoE for an Acetyl Cholinesterase Inhibitor: Galantamine HBr

• Published in: Chromatographia Vol. 73; no. 7-8; pp. 639 - 648
• Main Authors: Deshpande, Girish R., Roy, Amrendra K., Rao, N. Someswara, Rao, B. Mallikarjuna, Rudraprasad Reddy, J.
• Format: Journal Article
• Language: English
• Published: Wiesbaden Vieweg Verlag 01.04.2011; Springer
• Subjects: Analysis; Analytical Chemistry; Biological and medical sciences; Chemistry; Chemistry and Materials Science; Chromatography; General pharmacology; Laboratory Medicine; Medical sciences; Original; Pharmacology. Drug treatments; Pharmacy; Proteomics; Acetylcholinesterase inhibitor (AChEI); Ultra high performance liquid chromatography (UHPLC); Alzheimer’s disease (AD); Volatile ion-pair reagents; Design of experiments (DoE); Ultra performance liquid chromatography; Chemical analysis; Galantamine; Alzheimer's disease (AD); Esterases; Acetylcholinesterase; Mobile phase; Optimization; Alkaloid; Basic compound; Rivastigmine; Donepezil; Piperidine derivatives; Anticholinesterase agent; Volatile compound; Enzyme; Ion pair; Enzyme inhibitor; Antialzheimer agent; Carboxylic ester hydrolases; Ultraviolet detector; Experimental design; Hydrolases; Chemometrics
• ISSN: 0009-5893; 1612-1112
• DOI: 10.1007/s10337-011-1970-1

As over 70% of pharmaceutical compounds are bases, the analysis of these basic compounds by high performance liquid chromatography (HPLC) continues to be of great value and interesting. Acetyl cholinesterase inhibitors (AChEIs), which contain the basic compounds like Rivastigmine tartrate, Galantamine hydrobromide and Donepezil with different polarities, were chosen for the study. A rapid screening of the volatile ion-pairing reagents was performed using modern techniques like ultra high performance liquid chromatography (UHPLC). The experiments were planned using the ‘Design of Experiments’ (DoE) approach to identify the LC–MS compatible ion-pair reagent. In this study, Heptafluorobutyric acid (HFBA) has given a very good peak shape with tailing factor at 1.4 and theoretical plates up to ~5,000 were observed, compared to tailing factor at 1.9 and theoretical plates up to ~3,000 with non-volatile ion-pair reagent sodium heptane sulphonate (SHS). Similarly retention with HFBA was optimum as ~5 min in short run time method compared to ~13 min with SHS. This ion-pair reagent has proved to be good replacement of sodium alkyl sulphonate modifiers. HFBA can also be used for semi-preparative work for isolation of impurities by just evaporating the solvents. It avoids the extraction of other inorganic modifiers.