Determination of inorganic pharmaceutical counterions using hydrophilic interaction chromatography coupled with a Corona® CAD detector

A simple generic approach was investigated for the determination of inorganic pharmaceutical counterions in drug substances using conventional high performance liquid chromatographic (HPLC) instruments. An intuitive approach combined Corona® charged aerosol detection (CAD) with a polymer-based zwitterionic stationary phase in the hydrophilic interaction chromatography (HILIC) mode. Two generic methods based on this HILIC/CAD technique were developed to quantitate counterions such as Cl−, Br−, SO42−, K+, Ca2+ and Mg2+ in different pharmaceutical compounds. The development and capability of this HILIC/CAD technique analysis were examined.HILIC/CAD was compared to ion chromatography (IC), the most commonly used methodology for pharmaceutical counterion analysis. HILIC/CAD was found to have significant advantages in terms of: (1) being able to quantitate both anions and cations simultaneously without a need to change column/eluent or detection mode; (2) imposing much less restriction on the allowable organic percentage of the eluents than IC, and therefore being more appropriate for analysis of counterions of poorly water-soluble drugs; (3) requiring minimal training of the operating analysts. The precision and accuracy of counterion analysis using HILIC/CAD was not compromised. A typical precision of <2.0% was observed for all tested inorganic counterions; the determinations were within 2.0% relative to the theoretical counterion amount in the drug substance. Additionally, better accuracy was shown for Cl− in several drug substances as compared to IC. The main drawback of HILIC/CAD is its unsuitability for many of the current silica-based HILIC columns, because slight dissolution of silica leads to high baseline noise in the CAD detector.As a result of the universal detection characteristics of Corona® CAD and the unique separation capabilities of a zwitterionic stationary phase, an intuitive and robust HPLC method was developed for the generic determination of various counterions in different drug substances. HILIC/CAD technique is a useful alternative methodology, particularly for determination of counterions in low-solubility drugs.