Nonaqueous electrokinetic chromatography-electrospray ionization mass spectrometry using anionic cyclodextrins

Area of Science:

• Analytical Chemistry
• Separation Science
• Mass Spectrometry

Background:

• Development of online coupling methods for enhanced analytical capabilities.
• Challenges in combining capillary electrophoresis with mass spectrometry, particularly nonaqueous variants.
• Need for effective chiral and achiral separation techniques for complex mixtures.

Purpose of the Study:

• To establish and optimize an online nonaqueous electrokinetic chromatography-electrospray ionization mass spectrometry (NAEKC-ESI-MS) system.
• To evaluate the use of specific anionic cyclodextrin derivatives for chiral and achiral separations.
• To investigate and mitigate ionization suppression effects for improved detection limits.

Main Methods:

• Coupling of nonaqueous electrokinetic chromatography (NAEKC) with electrospray ionization mass spectrometry (ESI-MS).
• Utilized anionic cyclodextrins: heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin (HDMS-beta-CD) and heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-cyclodextrin (HDAS-beta-CD).
• Optimization of system parameters including sheath liquid, gas flow, temperature, and capillary position.
• Addition of camphorsulfonate to enhance chiral selectivity.

Main Results:

• Successful online coupling of NAEKC with ESI-MS for separation of positively charged analytes.
• Demonstrated sub-microg/ml detection limits despite observed ionization suppression from cyclodextrin counterions.
• Optimized parameters, particularly low nebulizing gas pressure, improved sensitivity.
• Enhanced chiral selectivity achieved through background electrolyte modification.

Conclusions:

• The developed NAEKC-ESI-MS system is effective for both chiral and achiral separations of positively charged compounds.
• The system demonstrates significant potential for drug profiling applications, including stereoisomers.
• Further optimization can overcome challenges like ionization suppression, broadening the applicability of the technique.