Performance of charged aerosol detection with hydrophilic interaction chromatography

Abstract

The performance of the charged aerosol detector (CAD) was investigated using a diverse set of 29 solutes, including acids, bases and neutrals, over a range of mobile phase compositions, particularly with regard to its suitability for use in hydrophilic interaction chromatography (HILIC). Flow injection analysis was employed as a rapid method to study detector performance. CAD response was 'quasi-universal', strong signals were observed for compounds that have low volatility at typical operating (room) temperature. For relatively involatile solutes, response was reasonably independent of solute chemistry, giving variation of 12-18% RSD from buffered 95% ACN (HILIC) to 10% ACN (RP). Somewhat higher response was obtained for basic compared with neutral solutes. For cationic basic solutes, use of anionic reagents of increasing size in the mobile phase (formic, trifluoroacetic and heptafluorobutyric acid) produced somewhat increased detector response, suggesting that salt formation with these reagents is contributory. However, the increase was not stoichiometric, pointing to a complex mechanism. In general, CAD response increased as the concentration of acetonitrile in the mobile phase was increased from highly aqueous (10% ACN) to values typical in the HILIC range (80-95% ACN), with signal to noise ratios about four times higher than those for the RP range. The response of the CAD is non-linear. Equations describing aerosol formation cannot entirely explain the shape of the plots. Limits of detection (determined with a column for solutes of low k) under HILIC conditions were of the order of 1-3ng on column, which compares favourably with other universal detectors. CAD response to inorganic anions allows observation of the independent movement through the column of the cationic and anionic constituents of basic drugs, which appear to be accompanied by mobile phase counterions, even at quite high solute concentrations.

Retention characteristics of some antibiotic and anti-retroviral compounds in hydrophilic interaction chromatography using isocratic elution, and gradient elution with repeatable partial equilibration

“…Furthermore, attempts at modelling retention [15,16] in HILIC have been made in order to facilitate optimisation and method development. HILIC has many advantages over RP such as improved desolvation and sensitivity with nebuliser-based detectors [17][18][19][20], lower operating pressures at a given linear velocity [6,21], superior peak shapes and column performance with basic compounds [6,22] as well as the possibility to achieve significantly different selectivity [23].…”

Semiquantitation of Paralytic Shellfish Toxins by Hydrophilic Interaction Liquid Chromatography-Mass Spectrometry Using Relative Molar Response Factors

“…Analyte response is inherently nonlinear using CAD, but a linear approximation can be used for calibration over small concentration ranges (<1 µg on column), [ 34 , 35 ] which was done here for PSTs, with good R 2 values (≥0.996) observed ( Table S1 ). PST analogs contain between zero and two hydroxysulfate groups, which significantly impact their physical and chemical properties in solution and in the gas phase.…”

“…However, accurate quantitative NMR still typically requires mg quantities of pure toxin, which can be difficult to obtain for many compounds. Specialized LC detectors have been developed that provide the potential for equimolar response between wide ranges of analytes including chemiluminescent nitrogen detection (CLND) [31], evaporative light scattering (ELSD) [32] and charged aerosol detection (CAD) [33][34][35]. These allow for accurate quantitation of smaller amounts of material without access to authentic standards by using certified reference materials of other chemical substances as calibrants.…”

Corona charged aerosol detector non-uniform response factors of purified alcohol ethoxylated homologues using liquid chromatography

“…As announced in the introduction but also in section 2.2, the signal depends on the number of charges detected. They themselves depend on the accessible surface and therefore on the size of the particles formed during nebulization step [40]. Until now, no study was found to explain this behavior, only assumptions could be done.…”

“…As many aerosol processes, the HPLC-CAD's response is influenced by the diameter of the generated particles. In their work, Russell et al explained the relationship between the analyte concentration and the size of the particles [40]. The size of the aerosol particles depends on several factors such as the viscosity of the mobile phase, its density, etc.…”