Exploration of the effects of chloride ions on the analysis of polar compounds at low concentrations by hydrophilic interaction liquid chromatography coupled to a charged aerosol detector: Application to tromethamine

Abstract

In this study, we discuss the origin of the slightly increased response of the charged aerosol detector when low-concentration polar drugs formulated with sodium chloride are analyzed by hydrophilic interaction liquid chromatography coupled to the charged aerosol detector. In the case of tromethamine mixed with saline solutions, we investigated several levels including the mobile phase, sample matrix, and detection. We show that the analysis of the rich-salted sample results in both interactions with the mobile phase modifiers and the stationary phase during the run time. With 150 mM NaCl as a compounding solution, a slight increase in the tromethamine peak area was observed (<5.5%). Our study suggests that chloride ions in excess sequentially interact firstly with the counterions from the organic modifiers and secondly with the analyte via the stationary phase and the contribution of hydrophilic interaction liquid chromatography retention mechanisms. Because of these effects, the hydrophilic interaction liquid chromatography-charged aerosol detector analysis of drugs in saline solutions requires particular attention, and a correction factor for quantitative purposes that accounts for formulation ions remains appropriate.

An optimization strategy for charged aerosol detection to linearize the detector response in the multicomponent quantitative analysis of Qishen Yiqi dripping pills

“…Accurately characterizing the relationship between the analytical signal and standard concentration dramatically influences the accuracy and precision of estimating unknown concentrations. In the HPLC-CAD method, linear regression equation parameters, including the intercept and slope, were usually determined using the OLSM [31,32]. OLSM aims to minimize the sum of squared deviations between observed values and their corresponding estimates from the regression equation, indicating equal weight to the absolute error at each concentration point.…”

Investigational Study of Mesalamine Dissolution Discrepancy: Utilization of Hyphenated Ultrahigh Performance Liquid Chromatography‐Charged Aerosol Detection‐High‐Resolution Mass Spectrometry

“…On the other hand, techniques like charged aerosol detector (CAD), which is an aerosol-based detector, offer sensitive, universal detection with near-to-uniform response [5]. CAD can detect all non-volatile, and many semi-volatile analytes, having a wider application for instance; analysis of pharmaceuticals (large and small molecule), biomolecules, food and beverages, surfactants, complex excipients and emulsifiers, lipids, polymers, and so on [6][7][8]. Liquid chromatography (LC)-CAD has been increasingly recognized for quantitative applications of complex multicomponent drugs and complex component analysis [9,10].…”